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Lung Cancer Screening Is the Push Smokers Need to Quit
Quitting smoking is challenging, particularly when resources are limited. A recent study in the United States confirmed that an intensive program combining behavioral therapy and medication, linked to a lung cancer screening program, offers the highest success rate. However, its long-term success was similar to that of telephone counseling and drug therapy.
Pulmonologist and experienced smoking cessation specialist from Stuttgart, Germany, Alexander Rupp, MD, emphasized the importance of leveraging routine healthcare interactions to encourage smoking cessation. “Although every doctor-patient contact offers the opportunity to discuss the risks of smoking and the opportunities for smoking cessation, the ‘window of opportunity’ is very wide, especially during lung cancer screening,” he said.
Germany is preparing to launch a lung cancer screening program for high-risk individuals, primarily current smokers and former smokers. Following the establishment of radiation protection regulations for such a program last year, the German Federal Joint Committee is currently working on its design. The initiative could be a game-changer for smoking cessation.
Lung cancer screening has been available for smokers in the United States for some time. Paul M. Cinciripini, PhD, and colleagues from the University of Texas MD Anderson Cancer Center, Houston, examined three smoking cessation strategies with decreasing treatment intensity among screening participants.
Unique Opportunity
Previous studies have shown that participation in a lung cancer screening program — typically offered only to high-risk individuals — significantly increases motivation to quit smoking.
“Repeated contact with doctors, repeated CT scans, and especially the findings that require monitoring all contribute to this effect,” explained Rupp, who regularly offers smoking cessation courses.
It has long been known how smoking cessation works best. “The gold standard is a combination of behavioral therapy support and drug treatment — if there is an addiction and withdrawal symptoms occur after quitting, which is the case for the majority of smokers,” Rupp explained.
The US study reinforced what is already well known: More intensive treatment approaches lead to higher quit rates.
“We know that the more intensively we look after smokers, the higher the quit rate. This applies in both areas: The more therapy sessions we do and the more often we prescribe medication, the more likely the patients are to succeed in remaining abstinent,” Rupp said.
However, resources for intensive smoking cessation programs are limited. A database maintained by the German Cancer Research Center and the German Federal Center for Health Education lists only 455 providers of smoking cessation courses in Germany, “not all of which even work on an evidence-based basis,” Rupp emphasized. Given that there are around 16 million smokers in Germany, there is an urgent need for smoking cessation programs that are less resource-intensive.
Intensity Variations
The US study compared three smoking cessation strategies of varying intensities, integrating behavioral counseling and medication.
Group 1: An integrated program with eight behavioral therapy sessions and 10-12 weeks of nicotine replacement therapy or medication (bupropion or varenicline).
Group 2: Lighter version of the integrated program. It consisted of four telephone consultations, written materials, online support, and 12 weeks of nicotine replacement therapy or medication prescribed by a radiologist.
Group 3: The least intensive approach, with 12 weeks of nicotine replacement therapy alone.
Each strategy was evaluated in 210 lung cancer screening participants aged 55-64 years who smoked an average of 15-20 cigarettes per day.
After 3 months, significantly more participants in the most intensive program (Group 1, 37.1%) had quit smoking than those in the other two groups (Group 2, 27.1%; Group 3, 25.2%).
But after 6 months, the difference between Groups 1 and 2 was not significant. The quit rates were as follows: Group 1, 32.4%; Group 2, 27.6%; and Group 3, 20.5%.
“It can be concluded from these results that the intensity of smoking cessation can be reduced to a certain extent as long as the combination of behavioral counseling and medication is given,” Rupp concluded.
Digital Solutions
Another new possibility, which was not examined in the US study, is digital health applications.
Smoke Free is a digital health application that provides behavioral therapy support for smoking cessation and is available in both German and English. Designed to replicate structured smoking cessation programs and offers an accessible alternative for individuals seeking to quit smoking.
Rupp emphasized the potential of digital tools like Smoke Free to expand access to effective smoking cessation strategies, particularly for those unable to attend in-person programs. While traditional cessation programs are limited in availability, digital apps can increase engagement in and adherence to smoking cessation efforts.
However, the biggest hurdle is smokers’ procrastination: “If you make smokers an offer, they usually do not take action afterward because they are caught in their ambivalence about whether they should quit or not.”
Policy Implications
This makes smoking cessation a mandatory component of lung cancer screening in the future. “It’s about cancer, and patients are really afraid of that,” Rupp advocated.
In a position paper, the German Respiratory Society, supported by multiple medical societies, has called for smoking cessation to be integrated into lung cancer screening protocols, with full coverage of counseling and medication by health insurance.
“Smoking cessation must be a mandatory component. If a participant in the lung cancer screening does not want this, then he or she must actively object,” stressed Rupp, lead author of the position paper. Also, the costs of smoking cessation, including those of withdrawal-inhibiting medication, must be fully covered by statutory health insurance, which has not been the case to date.
“That’s the only thing that makes sense. You can’t deny an addict access to proven treatments, especially when we know that a smoker who quits spontaneously without support has a relapse rate of 95%-97%, and the medication per se increases the quit rate by a factor of two or three,” Rupp concluded.
This story was translated and adapted from Medscape’s German edition using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.
Quitting smoking is challenging, particularly when resources are limited. A recent study in the United States confirmed that an intensive program combining behavioral therapy and medication, linked to a lung cancer screening program, offers the highest success rate. However, its long-term success was similar to that of telephone counseling and drug therapy.
Pulmonologist and experienced smoking cessation specialist from Stuttgart, Germany, Alexander Rupp, MD, emphasized the importance of leveraging routine healthcare interactions to encourage smoking cessation. “Although every doctor-patient contact offers the opportunity to discuss the risks of smoking and the opportunities for smoking cessation, the ‘window of opportunity’ is very wide, especially during lung cancer screening,” he said.
Germany is preparing to launch a lung cancer screening program for high-risk individuals, primarily current smokers and former smokers. Following the establishment of radiation protection regulations for such a program last year, the German Federal Joint Committee is currently working on its design. The initiative could be a game-changer for smoking cessation.
Lung cancer screening has been available for smokers in the United States for some time. Paul M. Cinciripini, PhD, and colleagues from the University of Texas MD Anderson Cancer Center, Houston, examined three smoking cessation strategies with decreasing treatment intensity among screening participants.
Unique Opportunity
Previous studies have shown that participation in a lung cancer screening program — typically offered only to high-risk individuals — significantly increases motivation to quit smoking.
“Repeated contact with doctors, repeated CT scans, and especially the findings that require monitoring all contribute to this effect,” explained Rupp, who regularly offers smoking cessation courses.
It has long been known how smoking cessation works best. “The gold standard is a combination of behavioral therapy support and drug treatment — if there is an addiction and withdrawal symptoms occur after quitting, which is the case for the majority of smokers,” Rupp explained.
The US study reinforced what is already well known: More intensive treatment approaches lead to higher quit rates.
“We know that the more intensively we look after smokers, the higher the quit rate. This applies in both areas: The more therapy sessions we do and the more often we prescribe medication, the more likely the patients are to succeed in remaining abstinent,” Rupp said.
However, resources for intensive smoking cessation programs are limited. A database maintained by the German Cancer Research Center and the German Federal Center for Health Education lists only 455 providers of smoking cessation courses in Germany, “not all of which even work on an evidence-based basis,” Rupp emphasized. Given that there are around 16 million smokers in Germany, there is an urgent need for smoking cessation programs that are less resource-intensive.
Intensity Variations
The US study compared three smoking cessation strategies of varying intensities, integrating behavioral counseling and medication.
Group 1: An integrated program with eight behavioral therapy sessions and 10-12 weeks of nicotine replacement therapy or medication (bupropion or varenicline).
Group 2: Lighter version of the integrated program. It consisted of four telephone consultations, written materials, online support, and 12 weeks of nicotine replacement therapy or medication prescribed by a radiologist.
Group 3: The least intensive approach, with 12 weeks of nicotine replacement therapy alone.
Each strategy was evaluated in 210 lung cancer screening participants aged 55-64 years who smoked an average of 15-20 cigarettes per day.
After 3 months, significantly more participants in the most intensive program (Group 1, 37.1%) had quit smoking than those in the other two groups (Group 2, 27.1%; Group 3, 25.2%).
But after 6 months, the difference between Groups 1 and 2 was not significant. The quit rates were as follows: Group 1, 32.4%; Group 2, 27.6%; and Group 3, 20.5%.
“It can be concluded from these results that the intensity of smoking cessation can be reduced to a certain extent as long as the combination of behavioral counseling and medication is given,” Rupp concluded.
Digital Solutions
Another new possibility, which was not examined in the US study, is digital health applications.
Smoke Free is a digital health application that provides behavioral therapy support for smoking cessation and is available in both German and English. Designed to replicate structured smoking cessation programs and offers an accessible alternative for individuals seeking to quit smoking.
Rupp emphasized the potential of digital tools like Smoke Free to expand access to effective smoking cessation strategies, particularly for those unable to attend in-person programs. While traditional cessation programs are limited in availability, digital apps can increase engagement in and adherence to smoking cessation efforts.
However, the biggest hurdle is smokers’ procrastination: “If you make smokers an offer, they usually do not take action afterward because they are caught in their ambivalence about whether they should quit or not.”
Policy Implications
This makes smoking cessation a mandatory component of lung cancer screening in the future. “It’s about cancer, and patients are really afraid of that,” Rupp advocated.
In a position paper, the German Respiratory Society, supported by multiple medical societies, has called for smoking cessation to be integrated into lung cancer screening protocols, with full coverage of counseling and medication by health insurance.
“Smoking cessation must be a mandatory component. If a participant in the lung cancer screening does not want this, then he or she must actively object,” stressed Rupp, lead author of the position paper. Also, the costs of smoking cessation, including those of withdrawal-inhibiting medication, must be fully covered by statutory health insurance, which has not been the case to date.
“That’s the only thing that makes sense. You can’t deny an addict access to proven treatments, especially when we know that a smoker who quits spontaneously without support has a relapse rate of 95%-97%, and the medication per se increases the quit rate by a factor of two or three,” Rupp concluded.
This story was translated and adapted from Medscape’s German edition using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.
Quitting smoking is challenging, particularly when resources are limited. A recent study in the United States confirmed that an intensive program combining behavioral therapy and medication, linked to a lung cancer screening program, offers the highest success rate. However, its long-term success was similar to that of telephone counseling and drug therapy.
Pulmonologist and experienced smoking cessation specialist from Stuttgart, Germany, Alexander Rupp, MD, emphasized the importance of leveraging routine healthcare interactions to encourage smoking cessation. “Although every doctor-patient contact offers the opportunity to discuss the risks of smoking and the opportunities for smoking cessation, the ‘window of opportunity’ is very wide, especially during lung cancer screening,” he said.
Germany is preparing to launch a lung cancer screening program for high-risk individuals, primarily current smokers and former smokers. Following the establishment of radiation protection regulations for such a program last year, the German Federal Joint Committee is currently working on its design. The initiative could be a game-changer for smoking cessation.
Lung cancer screening has been available for smokers in the United States for some time. Paul M. Cinciripini, PhD, and colleagues from the University of Texas MD Anderson Cancer Center, Houston, examined three smoking cessation strategies with decreasing treatment intensity among screening participants.
Unique Opportunity
Previous studies have shown that participation in a lung cancer screening program — typically offered only to high-risk individuals — significantly increases motivation to quit smoking.
“Repeated contact with doctors, repeated CT scans, and especially the findings that require monitoring all contribute to this effect,” explained Rupp, who regularly offers smoking cessation courses.
It has long been known how smoking cessation works best. “The gold standard is a combination of behavioral therapy support and drug treatment — if there is an addiction and withdrawal symptoms occur after quitting, which is the case for the majority of smokers,” Rupp explained.
The US study reinforced what is already well known: More intensive treatment approaches lead to higher quit rates.
“We know that the more intensively we look after smokers, the higher the quit rate. This applies in both areas: The more therapy sessions we do and the more often we prescribe medication, the more likely the patients are to succeed in remaining abstinent,” Rupp said.
However, resources for intensive smoking cessation programs are limited. A database maintained by the German Cancer Research Center and the German Federal Center for Health Education lists only 455 providers of smoking cessation courses in Germany, “not all of which even work on an evidence-based basis,” Rupp emphasized. Given that there are around 16 million smokers in Germany, there is an urgent need for smoking cessation programs that are less resource-intensive.
Intensity Variations
The US study compared three smoking cessation strategies of varying intensities, integrating behavioral counseling and medication.
Group 1: An integrated program with eight behavioral therapy sessions and 10-12 weeks of nicotine replacement therapy or medication (bupropion or varenicline).
Group 2: Lighter version of the integrated program. It consisted of four telephone consultations, written materials, online support, and 12 weeks of nicotine replacement therapy or medication prescribed by a radiologist.
Group 3: The least intensive approach, with 12 weeks of nicotine replacement therapy alone.
Each strategy was evaluated in 210 lung cancer screening participants aged 55-64 years who smoked an average of 15-20 cigarettes per day.
After 3 months, significantly more participants in the most intensive program (Group 1, 37.1%) had quit smoking than those in the other two groups (Group 2, 27.1%; Group 3, 25.2%).
But after 6 months, the difference between Groups 1 and 2 was not significant. The quit rates were as follows: Group 1, 32.4%; Group 2, 27.6%; and Group 3, 20.5%.
“It can be concluded from these results that the intensity of smoking cessation can be reduced to a certain extent as long as the combination of behavioral counseling and medication is given,” Rupp concluded.
Digital Solutions
Another new possibility, which was not examined in the US study, is digital health applications.
Smoke Free is a digital health application that provides behavioral therapy support for smoking cessation and is available in both German and English. Designed to replicate structured smoking cessation programs and offers an accessible alternative for individuals seeking to quit smoking.
Rupp emphasized the potential of digital tools like Smoke Free to expand access to effective smoking cessation strategies, particularly for those unable to attend in-person programs. While traditional cessation programs are limited in availability, digital apps can increase engagement in and adherence to smoking cessation efforts.
However, the biggest hurdle is smokers’ procrastination: “If you make smokers an offer, they usually do not take action afterward because they are caught in their ambivalence about whether they should quit or not.”
Policy Implications
This makes smoking cessation a mandatory component of lung cancer screening in the future. “It’s about cancer, and patients are really afraid of that,” Rupp advocated.
In a position paper, the German Respiratory Society, supported by multiple medical societies, has called for smoking cessation to be integrated into lung cancer screening protocols, with full coverage of counseling and medication by health insurance.
“Smoking cessation must be a mandatory component. If a participant in the lung cancer screening does not want this, then he or she must actively object,” stressed Rupp, lead author of the position paper. Also, the costs of smoking cessation, including those of withdrawal-inhibiting medication, must be fully covered by statutory health insurance, which has not been the case to date.
“That’s the only thing that makes sense. You can’t deny an addict access to proven treatments, especially when we know that a smoker who quits spontaneously without support has a relapse rate of 95%-97%, and the medication per se increases the quit rate by a factor of two or three,” Rupp concluded.
This story was translated and adapted from Medscape’s German edition using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.
Colorectal Cancer Awareness Month is Here!
Happy Colorectal Cancer (CRC) Awareness Month! Today, CRC is the third-most common cancer in men and women in the United States. But there’s good news: We know that screening saves lives. That’s why
We have a variety of resources for both physicians and patients to navigate the CRC screening process.
Clinical Guidance
AGA’s clinical guidelines and clinical practice updates provide evidence-based recommendations to guide your clinical practice decisions. Visit AGA’s new toolkit on CRC for the latest guidance on topics including colonoscopy follow-up, liquid biopsy, appropriate and tailored polypectomy, and more.
Patient Resources
AGA’s GI Patient Center can help your patients understand the need for CRC screening, colorectal cancer symptoms and risks, available screening tests, and the importance of preparing for a colonoscopy. Visit patient.gastro.org to access patient education materials.
Join the Conversation
We’ll be sharing resources and encouraging screenings on social media all month long. Join us as we remind everyone that 45 is the new 50.
Happy Colorectal Cancer (CRC) Awareness Month! Today, CRC is the third-most common cancer in men and women in the United States. But there’s good news: We know that screening saves lives. That’s why
We have a variety of resources for both physicians and patients to navigate the CRC screening process.
Clinical Guidance
AGA’s clinical guidelines and clinical practice updates provide evidence-based recommendations to guide your clinical practice decisions. Visit AGA’s new toolkit on CRC for the latest guidance on topics including colonoscopy follow-up, liquid biopsy, appropriate and tailored polypectomy, and more.
Patient Resources
AGA’s GI Patient Center can help your patients understand the need for CRC screening, colorectal cancer symptoms and risks, available screening tests, and the importance of preparing for a colonoscopy. Visit patient.gastro.org to access patient education materials.
Join the Conversation
We’ll be sharing resources and encouraging screenings on social media all month long. Join us as we remind everyone that 45 is the new 50.
Happy Colorectal Cancer (CRC) Awareness Month! Today, CRC is the third-most common cancer in men and women in the United States. But there’s good news: We know that screening saves lives. That’s why
We have a variety of resources for both physicians and patients to navigate the CRC screening process.
Clinical Guidance
AGA’s clinical guidelines and clinical practice updates provide evidence-based recommendations to guide your clinical practice decisions. Visit AGA’s new toolkit on CRC for the latest guidance on topics including colonoscopy follow-up, liquid biopsy, appropriate and tailored polypectomy, and more.
Patient Resources
AGA’s GI Patient Center can help your patients understand the need for CRC screening, colorectal cancer symptoms and risks, available screening tests, and the importance of preparing for a colonoscopy. Visit patient.gastro.org to access patient education materials.
Join the Conversation
We’ll be sharing resources and encouraging screenings on social media all month long. Join us as we remind everyone that 45 is the new 50.
New Risk Score Might Improve HCC Surveillance Among Cirrhosis Patients
, based to a recent phase 3 biomarker validation study.
The Prognostic Liver Secretome Signature with Alpha-Fetoprotein plus Age, Male Sex, Albumin-Bilirubin, and Platelets (PAaM) score integrates both molecular and clinical variables to effectively classify cirrhosis patients by their risk of developing HCC, potentially sparing low-risk patients from unnecessary surveillance, lead author Naoto Fujiwara, MD, PhD, of the University of Texas Southwestern Medical Center, Dallas, and colleagues reported.
“Hepatocellular carcinoma risk stratification is an urgent unmet need for cost-effective screening and early detection in patients with cirrhosis,” the investigators wrote in Gastroenterology. “This study represents the largest and first phase 3 biomarker validation study that establishes an integrative molecular/clinical score, PAaM, for HCC risk stratification.”
The PAaM score combines an 8-protein prognostic liver secretome signature with traditional clinical variables, including alpha-fetoprotein (AFP) levels, age, sex, albumin-bilirubin levels, and platelet counts. The score stratifies patients into high-, intermediate-, and low-risk categories.
The PAaM score was validated using 2 independent prospective cohorts in the United States: the statewide Texas Hepatocellular Carcinoma Consortium (THCCC) and the nationwide Hepatocellular Carcinoma Early Detection Strategy (HEDS). Across both cohorts, 3,484 patients with cirrhosis were followed over time to assess the development of HCC.
In the Texas cohort, comprising 2,156 patients with cirrhosis, PAaM classified 19% of patients as high risk, 42% as intermediate risk, and 39% as low risk. The annual incidence of HCC was significantly different across these groups, with high-risk patients experiencing a 5.3% incidence rate, versus 2.7% for intermediate-risk patients and 0.6% for low-risk patients (P less than .001). Compared with those in the low-risk group, high-risk patients had sub-distribution hazard ratio (sHR) of 7.51 for developing HCC, while intermediate-risk patients had an sHR of 4.20.
In the nationwide HEDS cohort, which included 1,328 patients, PAaM similarly stratified 15% of participants as high risk, 41% as intermediate risk, and 44% as low risk. Annual HCC incidence rates were 6.2%, 1.8%, and 0.8% for high-, intermediate-, and low-risk patients, respectively (P less than .001). Among these patients, sub-distribution hazard ratios for HCC were 6.54 for high-risk patients and 1.77 for intermediate-risk patients, again underscoring the tool’s potential to identify individuals at elevated risk of developing HCC.
The PAaM score outperformed existing models like the aMAP score and the PLSec-AFP molecular marker alone, with consistent superiority across a diverse range of cirrhosis etiologies, including metabolic dysfunction–associated steatotic liver disease (MASLD), alcohol-associated liver disease (ALD), and cured hepatitis C virus (HCV) infection.
Based on these findings, high-risk patients might benefit from more intensive screening strategies, Fujiwara and colleagues suggested, while intermediate-risk patients could continue with semi-annual ultrasound-based screening. Of note, low-risk patients—comprising about 40% of the study population—could potentially avoid frequent screenings, thus reducing healthcare costs and minimizing unnecessary interventions.
“This represents a significant step toward the clinical translation of an individual risk-based HCC screening strategy to improve early HCC detection and reduce HCC mortality,” the investigators concluded.This study was supported by various the National Cancer Institute, Veterans Affairs, the Japan Society for the Promotion of Science, and others. The investigators disclosed additional relationships with Boston Scientific, Sirtex, Bayer, and others.
Nancy S. Reau, MD, AGAF, of RUSH University in Chicago, highlighted both the promise and challenges of the PAaM score for HCC risk stratification, emphasizing that current liver cancer screening strategies remain inadequate, with only about 25% of patients receiving guideline-recommended surveillance.
“An easy-to-apply cost effective tool could significantly improve screening strategies, which should lead to earlier identification of liver cancer—at a time when curative treatment options are available,” Reau said.
PAaM, however, may be impractical for routine use.
“A tool that classifies people into 3 different screening strategies and requires longitudinal applications and re-classification could add complexity,” she explained, predicting that “clinicians aren’t going to use it correctly.
Reau was particularly concerned about the need for repeated assessments over time.
“People change,” she said. “A low-risk categorization by PAaM at the age of 40 may no longer be relevant at 50 or 60 as liver disease progresses.”
Although the tool is “exciting,” Reau suggested that it is also “premature” until appropriate reclassification intervals are understood.
She also noted that some patients still develop HCC despite being considered low risk, including cases of HCC that develop in non-cirrhotic HCV infection or MASLD.
Beyond the above clinical considerations, Dr. Reau pointed out several barriers to implementing PAaM in routine practice, starting with the under-recognition of cirrhosis. Even if patients are identified, ensuring both clinicians and patients adhere to screening recommendations remains a challenge.
Finally, financial considerations may pose obstacles.
“If some payers cover the tool and others do not, it will be very difficult to implement,” Dr. Reau concluded.
Reau reported no conflicts of interest.
Nancy S. Reau, MD, AGAF, of RUSH University in Chicago, highlighted both the promise and challenges of the PAaM score for HCC risk stratification, emphasizing that current liver cancer screening strategies remain inadequate, with only about 25% of patients receiving guideline-recommended surveillance.
“An easy-to-apply cost effective tool could significantly improve screening strategies, which should lead to earlier identification of liver cancer—at a time when curative treatment options are available,” Reau said.
PAaM, however, may be impractical for routine use.
“A tool that classifies people into 3 different screening strategies and requires longitudinal applications and re-classification could add complexity,” she explained, predicting that “clinicians aren’t going to use it correctly.
Reau was particularly concerned about the need for repeated assessments over time.
“People change,” she said. “A low-risk categorization by PAaM at the age of 40 may no longer be relevant at 50 or 60 as liver disease progresses.”
Although the tool is “exciting,” Reau suggested that it is also “premature” until appropriate reclassification intervals are understood.
She also noted that some patients still develop HCC despite being considered low risk, including cases of HCC that develop in non-cirrhotic HCV infection or MASLD.
Beyond the above clinical considerations, Dr. Reau pointed out several barriers to implementing PAaM in routine practice, starting with the under-recognition of cirrhosis. Even if patients are identified, ensuring both clinicians and patients adhere to screening recommendations remains a challenge.
Finally, financial considerations may pose obstacles.
“If some payers cover the tool and others do not, it will be very difficult to implement,” Dr. Reau concluded.
Reau reported no conflicts of interest.
Nancy S. Reau, MD, AGAF, of RUSH University in Chicago, highlighted both the promise and challenges of the PAaM score for HCC risk stratification, emphasizing that current liver cancer screening strategies remain inadequate, with only about 25% of patients receiving guideline-recommended surveillance.
“An easy-to-apply cost effective tool could significantly improve screening strategies, which should lead to earlier identification of liver cancer—at a time when curative treatment options are available,” Reau said.
PAaM, however, may be impractical for routine use.
“A tool that classifies people into 3 different screening strategies and requires longitudinal applications and re-classification could add complexity,” she explained, predicting that “clinicians aren’t going to use it correctly.
Reau was particularly concerned about the need for repeated assessments over time.
“People change,” she said. “A low-risk categorization by PAaM at the age of 40 may no longer be relevant at 50 or 60 as liver disease progresses.”
Although the tool is “exciting,” Reau suggested that it is also “premature” until appropriate reclassification intervals are understood.
She also noted that some patients still develop HCC despite being considered low risk, including cases of HCC that develop in non-cirrhotic HCV infection or MASLD.
Beyond the above clinical considerations, Dr. Reau pointed out several barriers to implementing PAaM in routine practice, starting with the under-recognition of cirrhosis. Even if patients are identified, ensuring both clinicians and patients adhere to screening recommendations remains a challenge.
Finally, financial considerations may pose obstacles.
“If some payers cover the tool and others do not, it will be very difficult to implement,” Dr. Reau concluded.
Reau reported no conflicts of interest.
, based to a recent phase 3 biomarker validation study.
The Prognostic Liver Secretome Signature with Alpha-Fetoprotein plus Age, Male Sex, Albumin-Bilirubin, and Platelets (PAaM) score integrates both molecular and clinical variables to effectively classify cirrhosis patients by their risk of developing HCC, potentially sparing low-risk patients from unnecessary surveillance, lead author Naoto Fujiwara, MD, PhD, of the University of Texas Southwestern Medical Center, Dallas, and colleagues reported.
“Hepatocellular carcinoma risk stratification is an urgent unmet need for cost-effective screening and early detection in patients with cirrhosis,” the investigators wrote in Gastroenterology. “This study represents the largest and first phase 3 biomarker validation study that establishes an integrative molecular/clinical score, PAaM, for HCC risk stratification.”
The PAaM score combines an 8-protein prognostic liver secretome signature with traditional clinical variables, including alpha-fetoprotein (AFP) levels, age, sex, albumin-bilirubin levels, and platelet counts. The score stratifies patients into high-, intermediate-, and low-risk categories.
The PAaM score was validated using 2 independent prospective cohorts in the United States: the statewide Texas Hepatocellular Carcinoma Consortium (THCCC) and the nationwide Hepatocellular Carcinoma Early Detection Strategy (HEDS). Across both cohorts, 3,484 patients with cirrhosis were followed over time to assess the development of HCC.
In the Texas cohort, comprising 2,156 patients with cirrhosis, PAaM classified 19% of patients as high risk, 42% as intermediate risk, and 39% as low risk. The annual incidence of HCC was significantly different across these groups, with high-risk patients experiencing a 5.3% incidence rate, versus 2.7% for intermediate-risk patients and 0.6% for low-risk patients (P less than .001). Compared with those in the low-risk group, high-risk patients had sub-distribution hazard ratio (sHR) of 7.51 for developing HCC, while intermediate-risk patients had an sHR of 4.20.
In the nationwide HEDS cohort, which included 1,328 patients, PAaM similarly stratified 15% of participants as high risk, 41% as intermediate risk, and 44% as low risk. Annual HCC incidence rates were 6.2%, 1.8%, and 0.8% for high-, intermediate-, and low-risk patients, respectively (P less than .001). Among these patients, sub-distribution hazard ratios for HCC were 6.54 for high-risk patients and 1.77 for intermediate-risk patients, again underscoring the tool’s potential to identify individuals at elevated risk of developing HCC.
The PAaM score outperformed existing models like the aMAP score and the PLSec-AFP molecular marker alone, with consistent superiority across a diverse range of cirrhosis etiologies, including metabolic dysfunction–associated steatotic liver disease (MASLD), alcohol-associated liver disease (ALD), and cured hepatitis C virus (HCV) infection.
Based on these findings, high-risk patients might benefit from more intensive screening strategies, Fujiwara and colleagues suggested, while intermediate-risk patients could continue with semi-annual ultrasound-based screening. Of note, low-risk patients—comprising about 40% of the study population—could potentially avoid frequent screenings, thus reducing healthcare costs and minimizing unnecessary interventions.
“This represents a significant step toward the clinical translation of an individual risk-based HCC screening strategy to improve early HCC detection and reduce HCC mortality,” the investigators concluded.This study was supported by various the National Cancer Institute, Veterans Affairs, the Japan Society for the Promotion of Science, and others. The investigators disclosed additional relationships with Boston Scientific, Sirtex, Bayer, and others.
, based to a recent phase 3 biomarker validation study.
The Prognostic Liver Secretome Signature with Alpha-Fetoprotein plus Age, Male Sex, Albumin-Bilirubin, and Platelets (PAaM) score integrates both molecular and clinical variables to effectively classify cirrhosis patients by their risk of developing HCC, potentially sparing low-risk patients from unnecessary surveillance, lead author Naoto Fujiwara, MD, PhD, of the University of Texas Southwestern Medical Center, Dallas, and colleagues reported.
“Hepatocellular carcinoma risk stratification is an urgent unmet need for cost-effective screening and early detection in patients with cirrhosis,” the investigators wrote in Gastroenterology. “This study represents the largest and first phase 3 biomarker validation study that establishes an integrative molecular/clinical score, PAaM, for HCC risk stratification.”
The PAaM score combines an 8-protein prognostic liver secretome signature with traditional clinical variables, including alpha-fetoprotein (AFP) levels, age, sex, albumin-bilirubin levels, and platelet counts. The score stratifies patients into high-, intermediate-, and low-risk categories.
The PAaM score was validated using 2 independent prospective cohorts in the United States: the statewide Texas Hepatocellular Carcinoma Consortium (THCCC) and the nationwide Hepatocellular Carcinoma Early Detection Strategy (HEDS). Across both cohorts, 3,484 patients with cirrhosis were followed over time to assess the development of HCC.
In the Texas cohort, comprising 2,156 patients with cirrhosis, PAaM classified 19% of patients as high risk, 42% as intermediate risk, and 39% as low risk. The annual incidence of HCC was significantly different across these groups, with high-risk patients experiencing a 5.3% incidence rate, versus 2.7% for intermediate-risk patients and 0.6% for low-risk patients (P less than .001). Compared with those in the low-risk group, high-risk patients had sub-distribution hazard ratio (sHR) of 7.51 for developing HCC, while intermediate-risk patients had an sHR of 4.20.
In the nationwide HEDS cohort, which included 1,328 patients, PAaM similarly stratified 15% of participants as high risk, 41% as intermediate risk, and 44% as low risk. Annual HCC incidence rates were 6.2%, 1.8%, and 0.8% for high-, intermediate-, and low-risk patients, respectively (P less than .001). Among these patients, sub-distribution hazard ratios for HCC were 6.54 for high-risk patients and 1.77 for intermediate-risk patients, again underscoring the tool’s potential to identify individuals at elevated risk of developing HCC.
The PAaM score outperformed existing models like the aMAP score and the PLSec-AFP molecular marker alone, with consistent superiority across a diverse range of cirrhosis etiologies, including metabolic dysfunction–associated steatotic liver disease (MASLD), alcohol-associated liver disease (ALD), and cured hepatitis C virus (HCV) infection.
Based on these findings, high-risk patients might benefit from more intensive screening strategies, Fujiwara and colleagues suggested, while intermediate-risk patients could continue with semi-annual ultrasound-based screening. Of note, low-risk patients—comprising about 40% of the study population—could potentially avoid frequent screenings, thus reducing healthcare costs and minimizing unnecessary interventions.
“This represents a significant step toward the clinical translation of an individual risk-based HCC screening strategy to improve early HCC detection and reduce HCC mortality,” the investigators concluded.This study was supported by various the National Cancer Institute, Veterans Affairs, the Japan Society for the Promotion of Science, and others. The investigators disclosed additional relationships with Boston Scientific, Sirtex, Bayer, and others.
FROM GASTROENTEROLOGY
Fecal Hemoglobin Levels From Negative FITs Signal CRC Risk
, according to a large international dose-response meta-analysis.
Although the association with neoplasia decreased as f-Hb levels rose, the findings support the development of risk-stratified screening strategies based on these concentrations, according to researchers led by Danica M.N. van den Berg, MSc, a PhD candidate and econometrics researcher in the Department of Public Health at Erasmus MC, University Medical Center in Rotterdam, the Netherlands.
Higher f-Hb concentrations in prior negative screening tests are strongly associated with an increased risk of detecting colorectal neoplasia in subsequent screenings, van den Berg said in an interview. “Gastroenterologists and other clinicians should consider the value of f-Hb concentrations in refining screening protocols and personalizing patient care to detect colorectal neoplasia earlier and more accurately.”
Published in Gastroenterology, the study was prompted by prior research showing individuals with f-Hb concentrations just below the positivity cutoff had an elevated CRC risk vs those with low or no f-Hb. “However, global variations in FIT positivity cutoffs and f-Hb category definitions complicated cross-study comparisons,” van den Berg said. Given the lack of an established dose-response relationship, the study aimed to clarify how f-Hb levels in previous screenings correlate with colorectal neoplasia detection. “Understanding this relationship is crucial for developing risk-stratified colorectal cancer screening strategies based on prior FIT results, which could improve the harm-benefit balance of screening,” she said.
According to van den Berg, f-Hb concentrations could help determine optimal CRC screening intervals by identifying higher-risk individuals who could benefit from more frequent testing, while those with lower concentrations could be screened less frequently.
Study Details
The systematic review and meta-analysis are the first to focus on the dose-response relationship between f-Hb levels in prior FIT screenings and colorectal neoplasia detection, van den Berg said. It included 13 ethnically diverse studies published during 2011-2023 with 4,493,223 individuals from Spain, France, the Netherlands, Taiwan, Denmark, Scotland, Ireland, Korea, Italy, and Norway. Most studies were cohort-based, and one was a randomized controlled trial.
All studies demonstrated a positive association between f-Hb in previous screenings and colorectal neoplasia detection. Almost all reported the f-Hb concentration measured in the prior screening round, while one study combined the f-Hb concentration of two previous screening rounds by using the cumulative f-Hb value. There was, however, wide variability in the stool positivity cut-offs in the included studies, ranging from 10 μg f-Hb/g to 80 μg f-Hb/g.
With an overall effect size of 0.69 (95% CI, 0.59-0.79), pooled analysis revealed that in the next screening round, individuals with f-Hb concentrations in stool of 5, 10, 20, and 40 μg/g had a threefold, fivefold, eightfold, and 13-fold higher risk for colorectal neoplasia, respectively, vs individuals showing 0 μg/g. Although there was significant study heterogeneity (I2 = 97.5%, P < .001), sensitivity analyses confirmed the consistency of findings. Interestingly, subgroup analyses indicated that f-Hb concentrations from a previous negative test were especially predictive of advanced neoplasia in subsequent screenings.
“This is a strategy worth pursuing and evaluating in the United States,” said gastroenterologist Theodore R. Levin, MD, a research scientist at Kaiser Permanente Division of Research in Northern California, commenting on the study but not involved in it. “However, there is no currently available FIT brand in the US that reports f-Hb concentration. All FITs in the US report as a qualitative positive-negative result.”
The Dutch investigation aligns with prior studies demonstrating a positive association between f-Hb concentrations in previous screenings and the detection of colorectal neoplasia. “Our working hypothesis was that risk increases in a decreasing manner as f-Hb concentrations rise, and the findings supported this hypothesis,” van den Berg said.
Other research has projected f-Hb level risk stratification to be effective and perhaps cost-effective in reducing delayed diagnosis of CRC.
Feasibility of Implementation
In large national screening programs in Europe, Asia, and Australia, as well as those of Kaiser Permanente and the Veterans Health Administration in the United States, information on f-Hb concentrations is already available.
“Therefore, incorporating an Hb-based approach should be relatively easy and affordable,” van den Berg said, and may help to optimize resource use while maintaining high detection rates. “However, the more critical question is whether such an approach would be acceptable to the target population.” To that end, randomized controlled trials in Italy and the Netherlands are offering tailored invitation intervals based on prior f-Hb concentrations and may provide insight into the real-world application of risk-stratified screening.
Among the many variables to be considered in the context of population-wide screening are cost-effectiveness, acceptability, and practicality, as well as invitation intervals, positivity cut-off levels, and start and stop ages for screening. “A key focus will be understanding the acceptability of risk-stratified colorectal cancer screening based on f-Hb among the target population and addressing any information needs they may have, as these are critical factors for successful implementation,” said van den Berg. Her group is currently studying the most effective and cost-effective risk-based strategy for CRC screening based on f-Hb levels.
The authors cautioned that since individuals with undetectable f-Hb levels make up the majority of those with negative FIT results, care must be taken that reducing screening frequency for this low-risk group does not lead to unfavorable outcomes at the population level.
This study was funded by the Dutch Organization for Scientific Research, which had no role in study design, data collection, analysis, interpretation, or writing.
The authors declared no competing interests. Levin disclosed no competing interests relevant to his comments.
A version of this article appeared on Medscape.com.
, according to a large international dose-response meta-analysis.
Although the association with neoplasia decreased as f-Hb levels rose, the findings support the development of risk-stratified screening strategies based on these concentrations, according to researchers led by Danica M.N. van den Berg, MSc, a PhD candidate and econometrics researcher in the Department of Public Health at Erasmus MC, University Medical Center in Rotterdam, the Netherlands.
Higher f-Hb concentrations in prior negative screening tests are strongly associated with an increased risk of detecting colorectal neoplasia in subsequent screenings, van den Berg said in an interview. “Gastroenterologists and other clinicians should consider the value of f-Hb concentrations in refining screening protocols and personalizing patient care to detect colorectal neoplasia earlier and more accurately.”
Published in Gastroenterology, the study was prompted by prior research showing individuals with f-Hb concentrations just below the positivity cutoff had an elevated CRC risk vs those with low or no f-Hb. “However, global variations in FIT positivity cutoffs and f-Hb category definitions complicated cross-study comparisons,” van den Berg said. Given the lack of an established dose-response relationship, the study aimed to clarify how f-Hb levels in previous screenings correlate with colorectal neoplasia detection. “Understanding this relationship is crucial for developing risk-stratified colorectal cancer screening strategies based on prior FIT results, which could improve the harm-benefit balance of screening,” she said.
According to van den Berg, f-Hb concentrations could help determine optimal CRC screening intervals by identifying higher-risk individuals who could benefit from more frequent testing, while those with lower concentrations could be screened less frequently.
Study Details
The systematic review and meta-analysis are the first to focus on the dose-response relationship between f-Hb levels in prior FIT screenings and colorectal neoplasia detection, van den Berg said. It included 13 ethnically diverse studies published during 2011-2023 with 4,493,223 individuals from Spain, France, the Netherlands, Taiwan, Denmark, Scotland, Ireland, Korea, Italy, and Norway. Most studies were cohort-based, and one was a randomized controlled trial.
All studies demonstrated a positive association between f-Hb in previous screenings and colorectal neoplasia detection. Almost all reported the f-Hb concentration measured in the prior screening round, while one study combined the f-Hb concentration of two previous screening rounds by using the cumulative f-Hb value. There was, however, wide variability in the stool positivity cut-offs in the included studies, ranging from 10 μg f-Hb/g to 80 μg f-Hb/g.
With an overall effect size of 0.69 (95% CI, 0.59-0.79), pooled analysis revealed that in the next screening round, individuals with f-Hb concentrations in stool of 5, 10, 20, and 40 μg/g had a threefold, fivefold, eightfold, and 13-fold higher risk for colorectal neoplasia, respectively, vs individuals showing 0 μg/g. Although there was significant study heterogeneity (I2 = 97.5%, P < .001), sensitivity analyses confirmed the consistency of findings. Interestingly, subgroup analyses indicated that f-Hb concentrations from a previous negative test were especially predictive of advanced neoplasia in subsequent screenings.
“This is a strategy worth pursuing and evaluating in the United States,” said gastroenterologist Theodore R. Levin, MD, a research scientist at Kaiser Permanente Division of Research in Northern California, commenting on the study but not involved in it. “However, there is no currently available FIT brand in the US that reports f-Hb concentration. All FITs in the US report as a qualitative positive-negative result.”
The Dutch investigation aligns with prior studies demonstrating a positive association between f-Hb concentrations in previous screenings and the detection of colorectal neoplasia. “Our working hypothesis was that risk increases in a decreasing manner as f-Hb concentrations rise, and the findings supported this hypothesis,” van den Berg said.
Other research has projected f-Hb level risk stratification to be effective and perhaps cost-effective in reducing delayed diagnosis of CRC.
Feasibility of Implementation
In large national screening programs in Europe, Asia, and Australia, as well as those of Kaiser Permanente and the Veterans Health Administration in the United States, information on f-Hb concentrations is already available.
“Therefore, incorporating an Hb-based approach should be relatively easy and affordable,” van den Berg said, and may help to optimize resource use while maintaining high detection rates. “However, the more critical question is whether such an approach would be acceptable to the target population.” To that end, randomized controlled trials in Italy and the Netherlands are offering tailored invitation intervals based on prior f-Hb concentrations and may provide insight into the real-world application of risk-stratified screening.
Among the many variables to be considered in the context of population-wide screening are cost-effectiveness, acceptability, and practicality, as well as invitation intervals, positivity cut-off levels, and start and stop ages for screening. “A key focus will be understanding the acceptability of risk-stratified colorectal cancer screening based on f-Hb among the target population and addressing any information needs they may have, as these are critical factors for successful implementation,” said van den Berg. Her group is currently studying the most effective and cost-effective risk-based strategy for CRC screening based on f-Hb levels.
The authors cautioned that since individuals with undetectable f-Hb levels make up the majority of those with negative FIT results, care must be taken that reducing screening frequency for this low-risk group does not lead to unfavorable outcomes at the population level.
This study was funded by the Dutch Organization for Scientific Research, which had no role in study design, data collection, analysis, interpretation, or writing.
The authors declared no competing interests. Levin disclosed no competing interests relevant to his comments.
A version of this article appeared on Medscape.com.
, according to a large international dose-response meta-analysis.
Although the association with neoplasia decreased as f-Hb levels rose, the findings support the development of risk-stratified screening strategies based on these concentrations, according to researchers led by Danica M.N. van den Berg, MSc, a PhD candidate and econometrics researcher in the Department of Public Health at Erasmus MC, University Medical Center in Rotterdam, the Netherlands.
Higher f-Hb concentrations in prior negative screening tests are strongly associated with an increased risk of detecting colorectal neoplasia in subsequent screenings, van den Berg said in an interview. “Gastroenterologists and other clinicians should consider the value of f-Hb concentrations in refining screening protocols and personalizing patient care to detect colorectal neoplasia earlier and more accurately.”
Published in Gastroenterology, the study was prompted by prior research showing individuals with f-Hb concentrations just below the positivity cutoff had an elevated CRC risk vs those with low or no f-Hb. “However, global variations in FIT positivity cutoffs and f-Hb category definitions complicated cross-study comparisons,” van den Berg said. Given the lack of an established dose-response relationship, the study aimed to clarify how f-Hb levels in previous screenings correlate with colorectal neoplasia detection. “Understanding this relationship is crucial for developing risk-stratified colorectal cancer screening strategies based on prior FIT results, which could improve the harm-benefit balance of screening,” she said.
According to van den Berg, f-Hb concentrations could help determine optimal CRC screening intervals by identifying higher-risk individuals who could benefit from more frequent testing, while those with lower concentrations could be screened less frequently.
Study Details
The systematic review and meta-analysis are the first to focus on the dose-response relationship between f-Hb levels in prior FIT screenings and colorectal neoplasia detection, van den Berg said. It included 13 ethnically diverse studies published during 2011-2023 with 4,493,223 individuals from Spain, France, the Netherlands, Taiwan, Denmark, Scotland, Ireland, Korea, Italy, and Norway. Most studies were cohort-based, and one was a randomized controlled trial.
All studies demonstrated a positive association between f-Hb in previous screenings and colorectal neoplasia detection. Almost all reported the f-Hb concentration measured in the prior screening round, while one study combined the f-Hb concentration of two previous screening rounds by using the cumulative f-Hb value. There was, however, wide variability in the stool positivity cut-offs in the included studies, ranging from 10 μg f-Hb/g to 80 μg f-Hb/g.
With an overall effect size of 0.69 (95% CI, 0.59-0.79), pooled analysis revealed that in the next screening round, individuals with f-Hb concentrations in stool of 5, 10, 20, and 40 μg/g had a threefold, fivefold, eightfold, and 13-fold higher risk for colorectal neoplasia, respectively, vs individuals showing 0 μg/g. Although there was significant study heterogeneity (I2 = 97.5%, P < .001), sensitivity analyses confirmed the consistency of findings. Interestingly, subgroup analyses indicated that f-Hb concentrations from a previous negative test were especially predictive of advanced neoplasia in subsequent screenings.
“This is a strategy worth pursuing and evaluating in the United States,” said gastroenterologist Theodore R. Levin, MD, a research scientist at Kaiser Permanente Division of Research in Northern California, commenting on the study but not involved in it. “However, there is no currently available FIT brand in the US that reports f-Hb concentration. All FITs in the US report as a qualitative positive-negative result.”
The Dutch investigation aligns with prior studies demonstrating a positive association between f-Hb concentrations in previous screenings and the detection of colorectal neoplasia. “Our working hypothesis was that risk increases in a decreasing manner as f-Hb concentrations rise, and the findings supported this hypothesis,” van den Berg said.
Other research has projected f-Hb level risk stratification to be effective and perhaps cost-effective in reducing delayed diagnosis of CRC.
Feasibility of Implementation
In large national screening programs in Europe, Asia, and Australia, as well as those of Kaiser Permanente and the Veterans Health Administration in the United States, information on f-Hb concentrations is already available.
“Therefore, incorporating an Hb-based approach should be relatively easy and affordable,” van den Berg said, and may help to optimize resource use while maintaining high detection rates. “However, the more critical question is whether such an approach would be acceptable to the target population.” To that end, randomized controlled trials in Italy and the Netherlands are offering tailored invitation intervals based on prior f-Hb concentrations and may provide insight into the real-world application of risk-stratified screening.
Among the many variables to be considered in the context of population-wide screening are cost-effectiveness, acceptability, and practicality, as well as invitation intervals, positivity cut-off levels, and start and stop ages for screening. “A key focus will be understanding the acceptability of risk-stratified colorectal cancer screening based on f-Hb among the target population and addressing any information needs they may have, as these are critical factors for successful implementation,” said van den Berg. Her group is currently studying the most effective and cost-effective risk-based strategy for CRC screening based on f-Hb levels.
The authors cautioned that since individuals with undetectable f-Hb levels make up the majority of those with negative FIT results, care must be taken that reducing screening frequency for this low-risk group does not lead to unfavorable outcomes at the population level.
This study was funded by the Dutch Organization for Scientific Research, which had no role in study design, data collection, analysis, interpretation, or writing.
The authors declared no competing interests. Levin disclosed no competing interests relevant to his comments.
A version of this article appeared on Medscape.com.
FROM GASTROENTEROLOGY
Headache Strongly Linked to Attempted, Completed Suicide
Headache, including migraine, tension-type, trigeminal autonomic cephalalgia (TAC), and posttraumatic stress headache are significantly associated with both attempted and completed suicide, results of a large study suggested.
The risk for attempted and completed suicide was more than threefold higher for individuals with posttraumatic headache and about twofold higher for those with TAC than their counterparts without headache.
Even those with tension-type headache, one of the milder headache types, carried nearly a twofold increased risk for attempted suicide vs the comparison group with no headache.
First author Holly Elser, MD, MPH, PhD, a resident physician in the Department of Neurology at the University of Pennsylvania, Philadelphia, told Medscape Medical News that the findings were “quite striking” and underscore the importance of screening for suicide risk even in patients with mild headache.
The findings were published online on February 3 in JAMA Neurology.
Common, Disabling
With an estimated global lifetime prevalence of 67%, headache disorders are a leading cause of productivity loss, work absences, and short-term disability.
The mechanisms linking headache disorders to suicide remain unclear for several reasons, the investigators noted.
First, the relationship between headache and psychiatric comorbidities may be complex and bidirectional, with psychiatric symptoms potentially exacerbating headache severity and frequency, the investigators noted.
Secondly, research has shown a consistent link between chronic pain and suicidality, even after adjusting for comorbid psychiatric conditions. Finally, disruptions in serotonergic pathways and increased production of inflammatory cytokines may contribute to both headache disorders and psychiatric symptoms, suggesting a shared biological basis.
The mechanisms linking headache disorders to suicide remain unclear for several reasons, the investigators noted.
First, the relationship between headache and psychiatric comorbidities may be complex and bidirectional, with psychiatric symptoms potentially exacerbating headache severity and frequency, the investigators noted.
Secondly, research has shown a consistent link between chronic pain and suicidality, even after adjusting for comorbid psychiatric conditions. Finally, disruptions in serotonergic pathways and increased production of inflammatory cytokines may contribute to both headache disorders and psychiatric symptoms, suggesting a shared biological basis.
“Patients diagnosed with headache with comorbid psychiatric symptoms may benefit in particular from comanagement with behavioral health specialists,” she added.
Not ‘Just Headaches’
In an interview with Medscape Medical News, Fred Cohen, MD, an assistant professor of medicine and neurology at the Icahn School of Medicine at Mount Sinai Hospital, New York City, shared his perspective on the findings. Cohen, who was not involved in the study agreed with Elser’s point and incorporated screening into his practice.
“As part of my routine at every new patient appointment, I conduct screenings for depression and suicide risk. If a patient responds affirmatively to any of these questions, I make sure they get connected to the mental health resources they need,” Cohen said.
At least one of his patients per week screens positive for depression, he noted.
“Primary headaches, including migraine and trigeminal autonomic cephalalgias, are a significant source of disability and suffering,” said Cohen, adding that migraine, in particular, is the leading cause of disability worldwide among women aged 18-50 years. “These conditions are often misunderstood and dismissed as ‘just headaches,’ when in reality, they are much more complex and debilitating.”
Given that depression and anxiety are common co-occurring conditions with primary headache disorders, he said, “depression screenings should be standard practice when evaluating patients with headaches.”
The study’s limitations include dependence on diagnosis codes, which are prone to misclassification, and lack of information about headache chronicity and severity, which could have affected the findings.
There was no information provided about study funding. Elser and Cohen reported no relevant financial relationships.
Headache, including migraine, tension-type, trigeminal autonomic cephalalgia (TAC), and posttraumatic stress headache are significantly associated with both attempted and completed suicide, results of a large study suggested.
The risk for attempted and completed suicide was more than threefold higher for individuals with posttraumatic headache and about twofold higher for those with TAC than their counterparts without headache.
Even those with tension-type headache, one of the milder headache types, carried nearly a twofold increased risk for attempted suicide vs the comparison group with no headache.
First author Holly Elser, MD, MPH, PhD, a resident physician in the Department of Neurology at the University of Pennsylvania, Philadelphia, told Medscape Medical News that the findings were “quite striking” and underscore the importance of screening for suicide risk even in patients with mild headache.
The findings were published online on February 3 in JAMA Neurology.
Common, Disabling
With an estimated global lifetime prevalence of 67%, headache disorders are a leading cause of productivity loss, work absences, and short-term disability.
The mechanisms linking headache disorders to suicide remain unclear for several reasons, the investigators noted.
First, the relationship between headache and psychiatric comorbidities may be complex and bidirectional, with psychiatric symptoms potentially exacerbating headache severity and frequency, the investigators noted.
Secondly, research has shown a consistent link between chronic pain and suicidality, even after adjusting for comorbid psychiatric conditions. Finally, disruptions in serotonergic pathways and increased production of inflammatory cytokines may contribute to both headache disorders and psychiatric symptoms, suggesting a shared biological basis.
The mechanisms linking headache disorders to suicide remain unclear for several reasons, the investigators noted.
First, the relationship between headache and psychiatric comorbidities may be complex and bidirectional, with psychiatric symptoms potentially exacerbating headache severity and frequency, the investigators noted.
Secondly, research has shown a consistent link between chronic pain and suicidality, even after adjusting for comorbid psychiatric conditions. Finally, disruptions in serotonergic pathways and increased production of inflammatory cytokines may contribute to both headache disorders and psychiatric symptoms, suggesting a shared biological basis.
“Patients diagnosed with headache with comorbid psychiatric symptoms may benefit in particular from comanagement with behavioral health specialists,” she added.
Not ‘Just Headaches’
In an interview with Medscape Medical News, Fred Cohen, MD, an assistant professor of medicine and neurology at the Icahn School of Medicine at Mount Sinai Hospital, New York City, shared his perspective on the findings. Cohen, who was not involved in the study agreed with Elser’s point and incorporated screening into his practice.
“As part of my routine at every new patient appointment, I conduct screenings for depression and suicide risk. If a patient responds affirmatively to any of these questions, I make sure they get connected to the mental health resources they need,” Cohen said.
At least one of his patients per week screens positive for depression, he noted.
“Primary headaches, including migraine and trigeminal autonomic cephalalgias, are a significant source of disability and suffering,” said Cohen, adding that migraine, in particular, is the leading cause of disability worldwide among women aged 18-50 years. “These conditions are often misunderstood and dismissed as ‘just headaches,’ when in reality, they are much more complex and debilitating.”
Given that depression and anxiety are common co-occurring conditions with primary headache disorders, he said, “depression screenings should be standard practice when evaluating patients with headaches.”
The study’s limitations include dependence on diagnosis codes, which are prone to misclassification, and lack of information about headache chronicity and severity, which could have affected the findings.
There was no information provided about study funding. Elser and Cohen reported no relevant financial relationships.
Headache, including migraine, tension-type, trigeminal autonomic cephalalgia (TAC), and posttraumatic stress headache are significantly associated with both attempted and completed suicide, results of a large study suggested.
The risk for attempted and completed suicide was more than threefold higher for individuals with posttraumatic headache and about twofold higher for those with TAC than their counterparts without headache.
Even those with tension-type headache, one of the milder headache types, carried nearly a twofold increased risk for attempted suicide vs the comparison group with no headache.
First author Holly Elser, MD, MPH, PhD, a resident physician in the Department of Neurology at the University of Pennsylvania, Philadelphia, told Medscape Medical News that the findings were “quite striking” and underscore the importance of screening for suicide risk even in patients with mild headache.
The findings were published online on February 3 in JAMA Neurology.
Common, Disabling
With an estimated global lifetime prevalence of 67%, headache disorders are a leading cause of productivity loss, work absences, and short-term disability.
The mechanisms linking headache disorders to suicide remain unclear for several reasons, the investigators noted.
First, the relationship between headache and psychiatric comorbidities may be complex and bidirectional, with psychiatric symptoms potentially exacerbating headache severity and frequency, the investigators noted.
Secondly, research has shown a consistent link between chronic pain and suicidality, even after adjusting for comorbid psychiatric conditions. Finally, disruptions in serotonergic pathways and increased production of inflammatory cytokines may contribute to both headache disorders and psychiatric symptoms, suggesting a shared biological basis.
The mechanisms linking headache disorders to suicide remain unclear for several reasons, the investigators noted.
First, the relationship between headache and psychiatric comorbidities may be complex and bidirectional, with psychiatric symptoms potentially exacerbating headache severity and frequency, the investigators noted.
Secondly, research has shown a consistent link between chronic pain and suicidality, even after adjusting for comorbid psychiatric conditions. Finally, disruptions in serotonergic pathways and increased production of inflammatory cytokines may contribute to both headache disorders and psychiatric symptoms, suggesting a shared biological basis.
“Patients diagnosed with headache with comorbid psychiatric symptoms may benefit in particular from comanagement with behavioral health specialists,” she added.
Not ‘Just Headaches’
In an interview with Medscape Medical News, Fred Cohen, MD, an assistant professor of medicine and neurology at the Icahn School of Medicine at Mount Sinai Hospital, New York City, shared his perspective on the findings. Cohen, who was not involved in the study agreed with Elser’s point and incorporated screening into his practice.
“As part of my routine at every new patient appointment, I conduct screenings for depression and suicide risk. If a patient responds affirmatively to any of these questions, I make sure they get connected to the mental health resources they need,” Cohen said.
At least one of his patients per week screens positive for depression, he noted.
“Primary headaches, including migraine and trigeminal autonomic cephalalgias, are a significant source of disability and suffering,” said Cohen, adding that migraine, in particular, is the leading cause of disability worldwide among women aged 18-50 years. “These conditions are often misunderstood and dismissed as ‘just headaches,’ when in reality, they are much more complex and debilitating.”
Given that depression and anxiety are common co-occurring conditions with primary headache disorders, he said, “depression screenings should be standard practice when evaluating patients with headaches.”
The study’s limitations include dependence on diagnosis codes, which are prone to misclassification, and lack of information about headache chronicity and severity, which could have affected the findings.
There was no information provided about study funding. Elser and Cohen reported no relevant financial relationships.
Clinical Research in Early Career Academic Medicine
Conducting clinical research as an early career gastroenterologist can take on many forms and has varying definitions of success. This article focuses on key factors to consider and should be supplemented with mentorship tailored to personal interests, goals, and institutional criteria for success. In this article, we will discuss selected high-yield topics that assist in early-career research. We will briefly discuss 1. Defining your niche, 2. Collaboration, 3. Visibility, 4. Time management, 5. Funding, 6. Receiving mentorship, and 7. Providing mentorship. We will conclude with discussing several authors’ experience in the research lab of the first author (FELD Lab – Fostering Equity in Liver and Digestive disease).
Defining Your Niche
Defining your niche is an essential component of an early career, as when academicians must transition from a trainee, who is supporting the research of an established mentor, to defining their own subspeciality area of investigation. Early-career academics should build on their prior work, but should also explore their own passions and skill set to define what will be unique about their research program and contributions to the field. Of course, positioning oneself at the intersection of two or more seemingly unrelated fields opens much opportunity for large impact but comes at a cost of identifying mentorship and justifying the niche to funders.
Collaboration
Fostering a collaborative environment is essential for early-career physician-researchers. One effective approach is to establish collaboration circles with other early career academics. Expanding research endeavors beyond a single institution to a multi-center framework enriches both scope and impact. This collaborative approach not only amplifies the depth of research but also facilitates peer mentorship and sponsorship. Participation in such networks can significantly enhance scholarly output and broaden professional reach during this critical phase of academic progression. Furthermore, prioritizing the promotion of colleagues within these networks is crucial. Proactive sponsorship opportunities, such as inviting peers to present at institutional seminars, strengthen both individual and collective academic visibility.
Collaboration is also essential to foster between trainees involved in early-career investigators’ work. An interconnected lab environment ensures that trainees remain informed about concurrent projects, thereby fostering a culture of shared knowledge and optimized productivity. Encouraging trainees to spearhead research aligned with their interests, under mentor guidance, nurtures independent inquiry and leadership. By establishing explicit roles, responsibilities, and authorship agreements at the outset of collaborative projects, early career mentors can avoid future conflicts and preserve a collaborative culture within the lab. This structured approach cultivates a supportive ecosystem, advancing both individual and collective research achievements.
Visibility
Establishing visibility and developing name recognition are crucial components of career advancement for early-career academic physicians. By clearly defining their areas of expertise, faculty can position themselves as leaders within their discipline. Active participation in professional societies, both at the local and national level, engagement with interest groups, and frequent contributions to educational events can be effective strategies for gaining recognition. Leveraging social media platforms can be helpful in enhancing visibility by facilitating connections and promoting research to a broader audience.
Moreover, research visibility plays a vital role in academic promotion. A strong publication record, reflected by an increasing h-index, demonstrates the impact and relevance of one’s research. Self-citation, when appropriate, can reinforce the continuity and progression of scholarly contributions. While publishing in high-impact journals is desirable, adaptability in resubmitting to other journals following rejections ensures that research remains visible and accessible. It also clearly establishes by whom the work was first done, before someone else investigates the line of inquiry. Through a combination of strategic engagement and publication efforts, early-career physicians can effectively build their professional reputation and advance their academic careers.
Time Management
Time management is essential for any research, and particularly in early career when efficiency in clinical care duties is still being gained. Securing protected time for research is essential to develop a niche, build connections (both institutionally and beyond their institutions), and demonstrate productivity that can be utilized to support future grant efforts.
Similarly, using protected time efficiently is required. Without organization and planning, research time can be spent with scattered meetings and responding to various tasks that do not directly support your research. It is helpful to be introspective about the time of the day you are most productive in your research efforts and blocking off that time to focus on research tasks and minimizing distractions. Blocking monthly time for larger scale thinking and planning is also important. Weekly lab and individual one-on-one meetings also support time management for trainees and lab members, to ensure efficiency and progress. Additionally, robust clinical support is essential to ensure that research time remains protected and patient care moves forward. When negotiating for positions, and in regular meetings thereafter, it is important to advocate for sufficient clinical staffing such that non-physician tasks can be appropriately delegated to another member of the care team.
Funding
Securing adequate funding poses a significant challenge for all early-career physician-scientists, particularly because of the discrepancy between National Institutes of Health salary caps and the higher average salaries in academic gastroenterology. This financial gap can deter physicians from pursuing research-intensive careers altogether and can derail early investigators who do not obtain funding rapidly. To overcome this, early-career investigators may need to adopt flexible strategies, such as accepting a lower salary that aligns with grant funding limits or funneling incentive or bonus pay to research accounts. Alternatively, they can advocate for institutional support to bridge the salary gap, ensuring their research efforts remain financially viable.
Institutions committed to fostering research excellence may offer supplemental funding or bridge programs to retain talented physician-scientists, thereby mitigating the financial strain and encouraging long-term engagement in research. Regular meetings to review salary and support sources, including philanthropy, foundation grants, and other streams, should be undertaken with leadership to align the researcher’s timeline and available funding. If career development funding appears untenable, consideration of multi–principal investigator R01s or equivalent with senior established investigators can be a promising path.
Receiving Mentorship
Effective mentorship for early-career physician-scientists should be approached through a team-based model that leverages both internal and external mentors. Internal mentors, familiar with the specific culture, expectations, and advancement pathways of the institution, can provide invaluable guidance on navigating institutional metrics for success, such as promotion criteria, grant acquisition, and clinical-research balance. External mentors, on the other hand, bring a broader perspective by offering innovative career development strategies and solutions derived from experiences at their home institutions. This multimodal mentorship model ensures a well-rounded approach to professional growth.
All national gastroenterology societies, including the American Gastroenterological Association, the American College of Gastroenterology, and the American Society for Gastrointestinal Endoscopy, and American Association for the Study of Liver Disease, offer structured early-career mentorship programs designed to connect emerging researchers with experienced leaders in the field (see below). These programs typically require a formal application process and are highly regarded for their exceptional quality and impact. Participation in such initiatives can significantly enhance career development by expanding networks, fostering interdisciplinary collaboration, and providing tailored guidance that complements institutional support. Integrating both internal and external mentorship opportunities ensures a robust and dynamic foundation for long-term success in academic medicine.
- AGA Career Compass (https://gastro.org/fellows-and-early-career/mentoring/)
- ACG Early Career Leadership Program (https://gi.org/acg-institute/early-career-leadership-program/)
- AGA-AASLD Academic Skills Workshop (https://gastro.org/news/applications-now-being-accepted-for-the-2024-aga-aasld-academic-skills-workshop/)
- AASLD Women’s Initiative Committee Leadership Program (https://www.aasld.org/promoting-leadership-potential-women-hepatology)
- Scrubs n Heels Mentorship Matrix (https://scrubsandheels.com/matrix/)
Providing Mentorship
The trainee authors on this manuscript describe in this section what has been helpful for them as mentees in the FELD research lab.
Student doctor Nguyen describes her experience as a lab member and things she finds most helpful as a medical student in the lab:
- Upon joining the team, a one-to-one meeting to discuss trainee’s personal and professional goals, and availability, was crucial to building the mentor-mentee relationship. Establishing this meaningful mentorship early on clarified expectations on both sides, built trust, and increased motivation. As a trainee, it is essential for me to see how my work aligns with a long-term goal and to receive ample guidance throughout the process.
- One of the most impactful experiences has been joining informal lunch sessions where trainees discussed data collection protocols and exchanged insights. In doing so, Dr. Feld has cultivated a lab culture that encourages curiosity, constructive feedback, and collaborative learning.
- To increase productivity, our team of trainees created a useful group message thread where we coordinated more sessions to collaborate. This coordination formed stronger relationships between team members and fostered a sense of shared purpose.
Dr. Cooper, a third year internal medicine resident, describes her experience as both a research mentee and a mentor to the junior trainees: “As a resident pursuing a career in academic gastroenterology and hepatology, I have found three key elements to be most helpful: intentional mentorship, structured meetings, and leadership development.”
- Intentional mentorship: Prior to joining the lab, I met with Dr. Feld to discuss my research experience and my goals. She took the time to understand these within the context of my training timeline and tailored project opportunities that aligned with my interests and were both feasible and impactful for my next steps. This intentional approach not only fostered a productive research experience but also established a mentor-mentee relationship built on genuine care for my growth and development.
- Regular meetings: Frequent lab meetings promote accountability, teamwork, and shared problem-solving skills. The open exchange of ideas fosters collaboration and joint problem solving to elevate the quality of our research. They are also an opportunity to observe key decision-making points during the research process and have been a great way to learn more about solid methodology.
- Supervised leadership: I have had ample time to lead discussions and coordinate projects among the junior trainees. These monitored leadership experiences promote project management skills, mentorship, and team dynamic awareness while maintaining the safety net of senior guidance. This model helped me transition from a trainee supporting others’ research to a more independent role, contributing to multi-disciplinary projects while mentoring junior members.
Conclusion
In conclusion, many exciting opportunities and notable barriers exist to establishing a clinical research laboratory in the early career. While excellence in each of the areas outlined may evolve, some aspects will come easier than others and with time, persistence, and a bit of luck, the research world will be a better place because of your contributions!
Dr. Feld is assistant professor of gastroenterology and hepatology and physician executive of Diversity, Equity, Inclusion and Belonging for the department of medicine at the University of Massachusetts (UMass) Chan Medical School, Worcester. Ms. Nguyen is a medical student at UMass Chan Medical School. Dr. Cooper is a resident physician at UMass Chan Medical School. Dr. Rabinowitz is an attending physician in the Inflammatory Bowel Disease Center at Beth Israel Deaconess Medical Center, Boston, Mass. Dr. Uchida is codirector of the Multidisciplinary Eosinophilic Gastrointestinal Disease Clinic at the University of Utah School of Medicine, Salt Lake City.
Conducting clinical research as an early career gastroenterologist can take on many forms and has varying definitions of success. This article focuses on key factors to consider and should be supplemented with mentorship tailored to personal interests, goals, and institutional criteria for success. In this article, we will discuss selected high-yield topics that assist in early-career research. We will briefly discuss 1. Defining your niche, 2. Collaboration, 3. Visibility, 4. Time management, 5. Funding, 6. Receiving mentorship, and 7. Providing mentorship. We will conclude with discussing several authors’ experience in the research lab of the first author (FELD Lab – Fostering Equity in Liver and Digestive disease).
Defining Your Niche
Defining your niche is an essential component of an early career, as when academicians must transition from a trainee, who is supporting the research of an established mentor, to defining their own subspeciality area of investigation. Early-career academics should build on their prior work, but should also explore their own passions and skill set to define what will be unique about their research program and contributions to the field. Of course, positioning oneself at the intersection of two or more seemingly unrelated fields opens much opportunity for large impact but comes at a cost of identifying mentorship and justifying the niche to funders.
Collaboration
Fostering a collaborative environment is essential for early-career physician-researchers. One effective approach is to establish collaboration circles with other early career academics. Expanding research endeavors beyond a single institution to a multi-center framework enriches both scope and impact. This collaborative approach not only amplifies the depth of research but also facilitates peer mentorship and sponsorship. Participation in such networks can significantly enhance scholarly output and broaden professional reach during this critical phase of academic progression. Furthermore, prioritizing the promotion of colleagues within these networks is crucial. Proactive sponsorship opportunities, such as inviting peers to present at institutional seminars, strengthen both individual and collective academic visibility.
Collaboration is also essential to foster between trainees involved in early-career investigators’ work. An interconnected lab environment ensures that trainees remain informed about concurrent projects, thereby fostering a culture of shared knowledge and optimized productivity. Encouraging trainees to spearhead research aligned with their interests, under mentor guidance, nurtures independent inquiry and leadership. By establishing explicit roles, responsibilities, and authorship agreements at the outset of collaborative projects, early career mentors can avoid future conflicts and preserve a collaborative culture within the lab. This structured approach cultivates a supportive ecosystem, advancing both individual and collective research achievements.
Visibility
Establishing visibility and developing name recognition are crucial components of career advancement for early-career academic physicians. By clearly defining their areas of expertise, faculty can position themselves as leaders within their discipline. Active participation in professional societies, both at the local and national level, engagement with interest groups, and frequent contributions to educational events can be effective strategies for gaining recognition. Leveraging social media platforms can be helpful in enhancing visibility by facilitating connections and promoting research to a broader audience.
Moreover, research visibility plays a vital role in academic promotion. A strong publication record, reflected by an increasing h-index, demonstrates the impact and relevance of one’s research. Self-citation, when appropriate, can reinforce the continuity and progression of scholarly contributions. While publishing in high-impact journals is desirable, adaptability in resubmitting to other journals following rejections ensures that research remains visible and accessible. It also clearly establishes by whom the work was first done, before someone else investigates the line of inquiry. Through a combination of strategic engagement and publication efforts, early-career physicians can effectively build their professional reputation and advance their academic careers.
Time Management
Time management is essential for any research, and particularly in early career when efficiency in clinical care duties is still being gained. Securing protected time for research is essential to develop a niche, build connections (both institutionally and beyond their institutions), and demonstrate productivity that can be utilized to support future grant efforts.
Similarly, using protected time efficiently is required. Without organization and planning, research time can be spent with scattered meetings and responding to various tasks that do not directly support your research. It is helpful to be introspective about the time of the day you are most productive in your research efforts and blocking off that time to focus on research tasks and minimizing distractions. Blocking monthly time for larger scale thinking and planning is also important. Weekly lab and individual one-on-one meetings also support time management for trainees and lab members, to ensure efficiency and progress. Additionally, robust clinical support is essential to ensure that research time remains protected and patient care moves forward. When negotiating for positions, and in regular meetings thereafter, it is important to advocate for sufficient clinical staffing such that non-physician tasks can be appropriately delegated to another member of the care team.
Funding
Securing adequate funding poses a significant challenge for all early-career physician-scientists, particularly because of the discrepancy between National Institutes of Health salary caps and the higher average salaries in academic gastroenterology. This financial gap can deter physicians from pursuing research-intensive careers altogether and can derail early investigators who do not obtain funding rapidly. To overcome this, early-career investigators may need to adopt flexible strategies, such as accepting a lower salary that aligns with grant funding limits or funneling incentive or bonus pay to research accounts. Alternatively, they can advocate for institutional support to bridge the salary gap, ensuring their research efforts remain financially viable.
Institutions committed to fostering research excellence may offer supplemental funding or bridge programs to retain talented physician-scientists, thereby mitigating the financial strain and encouraging long-term engagement in research. Regular meetings to review salary and support sources, including philanthropy, foundation grants, and other streams, should be undertaken with leadership to align the researcher’s timeline and available funding. If career development funding appears untenable, consideration of multi–principal investigator R01s or equivalent with senior established investigators can be a promising path.
Receiving Mentorship
Effective mentorship for early-career physician-scientists should be approached through a team-based model that leverages both internal and external mentors. Internal mentors, familiar with the specific culture, expectations, and advancement pathways of the institution, can provide invaluable guidance on navigating institutional metrics for success, such as promotion criteria, grant acquisition, and clinical-research balance. External mentors, on the other hand, bring a broader perspective by offering innovative career development strategies and solutions derived from experiences at their home institutions. This multimodal mentorship model ensures a well-rounded approach to professional growth.
All national gastroenterology societies, including the American Gastroenterological Association, the American College of Gastroenterology, and the American Society for Gastrointestinal Endoscopy, and American Association for the Study of Liver Disease, offer structured early-career mentorship programs designed to connect emerging researchers with experienced leaders in the field (see below). These programs typically require a formal application process and are highly regarded for their exceptional quality and impact. Participation in such initiatives can significantly enhance career development by expanding networks, fostering interdisciplinary collaboration, and providing tailored guidance that complements institutional support. Integrating both internal and external mentorship opportunities ensures a robust and dynamic foundation for long-term success in academic medicine.
- AGA Career Compass (https://gastro.org/fellows-and-early-career/mentoring/)
- ACG Early Career Leadership Program (https://gi.org/acg-institute/early-career-leadership-program/)
- AGA-AASLD Academic Skills Workshop (https://gastro.org/news/applications-now-being-accepted-for-the-2024-aga-aasld-academic-skills-workshop/)
- AASLD Women’s Initiative Committee Leadership Program (https://www.aasld.org/promoting-leadership-potential-women-hepatology)
- Scrubs n Heels Mentorship Matrix (https://scrubsandheels.com/matrix/)
Providing Mentorship
The trainee authors on this manuscript describe in this section what has been helpful for them as mentees in the FELD research lab.
Student doctor Nguyen describes her experience as a lab member and things she finds most helpful as a medical student in the lab:
- Upon joining the team, a one-to-one meeting to discuss trainee’s personal and professional goals, and availability, was crucial to building the mentor-mentee relationship. Establishing this meaningful mentorship early on clarified expectations on both sides, built trust, and increased motivation. As a trainee, it is essential for me to see how my work aligns with a long-term goal and to receive ample guidance throughout the process.
- One of the most impactful experiences has been joining informal lunch sessions where trainees discussed data collection protocols and exchanged insights. In doing so, Dr. Feld has cultivated a lab culture that encourages curiosity, constructive feedback, and collaborative learning.
- To increase productivity, our team of trainees created a useful group message thread where we coordinated more sessions to collaborate. This coordination formed stronger relationships between team members and fostered a sense of shared purpose.
Dr. Cooper, a third year internal medicine resident, describes her experience as both a research mentee and a mentor to the junior trainees: “As a resident pursuing a career in academic gastroenterology and hepatology, I have found three key elements to be most helpful: intentional mentorship, structured meetings, and leadership development.”
- Intentional mentorship: Prior to joining the lab, I met with Dr. Feld to discuss my research experience and my goals. She took the time to understand these within the context of my training timeline and tailored project opportunities that aligned with my interests and were both feasible and impactful for my next steps. This intentional approach not only fostered a productive research experience but also established a mentor-mentee relationship built on genuine care for my growth and development.
- Regular meetings: Frequent lab meetings promote accountability, teamwork, and shared problem-solving skills. The open exchange of ideas fosters collaboration and joint problem solving to elevate the quality of our research. They are also an opportunity to observe key decision-making points during the research process and have been a great way to learn more about solid methodology.
- Supervised leadership: I have had ample time to lead discussions and coordinate projects among the junior trainees. These monitored leadership experiences promote project management skills, mentorship, and team dynamic awareness while maintaining the safety net of senior guidance. This model helped me transition from a trainee supporting others’ research to a more independent role, contributing to multi-disciplinary projects while mentoring junior members.
Conclusion
In conclusion, many exciting opportunities and notable barriers exist to establishing a clinical research laboratory in the early career. While excellence in each of the areas outlined may evolve, some aspects will come easier than others and with time, persistence, and a bit of luck, the research world will be a better place because of your contributions!
Dr. Feld is assistant professor of gastroenterology and hepatology and physician executive of Diversity, Equity, Inclusion and Belonging for the department of medicine at the University of Massachusetts (UMass) Chan Medical School, Worcester. Ms. Nguyen is a medical student at UMass Chan Medical School. Dr. Cooper is a resident physician at UMass Chan Medical School. Dr. Rabinowitz is an attending physician in the Inflammatory Bowel Disease Center at Beth Israel Deaconess Medical Center, Boston, Mass. Dr. Uchida is codirector of the Multidisciplinary Eosinophilic Gastrointestinal Disease Clinic at the University of Utah School of Medicine, Salt Lake City.
Conducting clinical research as an early career gastroenterologist can take on many forms and has varying definitions of success. This article focuses on key factors to consider and should be supplemented with mentorship tailored to personal interests, goals, and institutional criteria for success. In this article, we will discuss selected high-yield topics that assist in early-career research. We will briefly discuss 1. Defining your niche, 2. Collaboration, 3. Visibility, 4. Time management, 5. Funding, 6. Receiving mentorship, and 7. Providing mentorship. We will conclude with discussing several authors’ experience in the research lab of the first author (FELD Lab – Fostering Equity in Liver and Digestive disease).
Defining Your Niche
Defining your niche is an essential component of an early career, as when academicians must transition from a trainee, who is supporting the research of an established mentor, to defining their own subspeciality area of investigation. Early-career academics should build on their prior work, but should also explore their own passions and skill set to define what will be unique about their research program and contributions to the field. Of course, positioning oneself at the intersection of two or more seemingly unrelated fields opens much opportunity for large impact but comes at a cost of identifying mentorship and justifying the niche to funders.
Collaboration
Fostering a collaborative environment is essential for early-career physician-researchers. One effective approach is to establish collaboration circles with other early career academics. Expanding research endeavors beyond a single institution to a multi-center framework enriches both scope and impact. This collaborative approach not only amplifies the depth of research but also facilitates peer mentorship and sponsorship. Participation in such networks can significantly enhance scholarly output and broaden professional reach during this critical phase of academic progression. Furthermore, prioritizing the promotion of colleagues within these networks is crucial. Proactive sponsorship opportunities, such as inviting peers to present at institutional seminars, strengthen both individual and collective academic visibility.
Collaboration is also essential to foster between trainees involved in early-career investigators’ work. An interconnected lab environment ensures that trainees remain informed about concurrent projects, thereby fostering a culture of shared knowledge and optimized productivity. Encouraging trainees to spearhead research aligned with their interests, under mentor guidance, nurtures independent inquiry and leadership. By establishing explicit roles, responsibilities, and authorship agreements at the outset of collaborative projects, early career mentors can avoid future conflicts and preserve a collaborative culture within the lab. This structured approach cultivates a supportive ecosystem, advancing both individual and collective research achievements.
Visibility
Establishing visibility and developing name recognition are crucial components of career advancement for early-career academic physicians. By clearly defining their areas of expertise, faculty can position themselves as leaders within their discipline. Active participation in professional societies, both at the local and national level, engagement with interest groups, and frequent contributions to educational events can be effective strategies for gaining recognition. Leveraging social media platforms can be helpful in enhancing visibility by facilitating connections and promoting research to a broader audience.
Moreover, research visibility plays a vital role in academic promotion. A strong publication record, reflected by an increasing h-index, demonstrates the impact and relevance of one’s research. Self-citation, when appropriate, can reinforce the continuity and progression of scholarly contributions. While publishing in high-impact journals is desirable, adaptability in resubmitting to other journals following rejections ensures that research remains visible and accessible. It also clearly establishes by whom the work was first done, before someone else investigates the line of inquiry. Through a combination of strategic engagement and publication efforts, early-career physicians can effectively build their professional reputation and advance their academic careers.
Time Management
Time management is essential for any research, and particularly in early career when efficiency in clinical care duties is still being gained. Securing protected time for research is essential to develop a niche, build connections (both institutionally and beyond their institutions), and demonstrate productivity that can be utilized to support future grant efforts.
Similarly, using protected time efficiently is required. Without organization and planning, research time can be spent with scattered meetings and responding to various tasks that do not directly support your research. It is helpful to be introspective about the time of the day you are most productive in your research efforts and blocking off that time to focus on research tasks and minimizing distractions. Blocking monthly time for larger scale thinking and planning is also important. Weekly lab and individual one-on-one meetings also support time management for trainees and lab members, to ensure efficiency and progress. Additionally, robust clinical support is essential to ensure that research time remains protected and patient care moves forward. When negotiating for positions, and in regular meetings thereafter, it is important to advocate for sufficient clinical staffing such that non-physician tasks can be appropriately delegated to another member of the care team.
Funding
Securing adequate funding poses a significant challenge for all early-career physician-scientists, particularly because of the discrepancy between National Institutes of Health salary caps and the higher average salaries in academic gastroenterology. This financial gap can deter physicians from pursuing research-intensive careers altogether and can derail early investigators who do not obtain funding rapidly. To overcome this, early-career investigators may need to adopt flexible strategies, such as accepting a lower salary that aligns with grant funding limits or funneling incentive or bonus pay to research accounts. Alternatively, they can advocate for institutional support to bridge the salary gap, ensuring their research efforts remain financially viable.
Institutions committed to fostering research excellence may offer supplemental funding or bridge programs to retain talented physician-scientists, thereby mitigating the financial strain and encouraging long-term engagement in research. Regular meetings to review salary and support sources, including philanthropy, foundation grants, and other streams, should be undertaken with leadership to align the researcher’s timeline and available funding. If career development funding appears untenable, consideration of multi–principal investigator R01s or equivalent with senior established investigators can be a promising path.
Receiving Mentorship
Effective mentorship for early-career physician-scientists should be approached through a team-based model that leverages both internal and external mentors. Internal mentors, familiar with the specific culture, expectations, and advancement pathways of the institution, can provide invaluable guidance on navigating institutional metrics for success, such as promotion criteria, grant acquisition, and clinical-research balance. External mentors, on the other hand, bring a broader perspective by offering innovative career development strategies and solutions derived from experiences at their home institutions. This multimodal mentorship model ensures a well-rounded approach to professional growth.
All national gastroenterology societies, including the American Gastroenterological Association, the American College of Gastroenterology, and the American Society for Gastrointestinal Endoscopy, and American Association for the Study of Liver Disease, offer structured early-career mentorship programs designed to connect emerging researchers with experienced leaders in the field (see below). These programs typically require a formal application process and are highly regarded for their exceptional quality and impact. Participation in such initiatives can significantly enhance career development by expanding networks, fostering interdisciplinary collaboration, and providing tailored guidance that complements institutional support. Integrating both internal and external mentorship opportunities ensures a robust and dynamic foundation for long-term success in academic medicine.
- AGA Career Compass (https://gastro.org/fellows-and-early-career/mentoring/)
- ACG Early Career Leadership Program (https://gi.org/acg-institute/early-career-leadership-program/)
- AGA-AASLD Academic Skills Workshop (https://gastro.org/news/applications-now-being-accepted-for-the-2024-aga-aasld-academic-skills-workshop/)
- AASLD Women’s Initiative Committee Leadership Program (https://www.aasld.org/promoting-leadership-potential-women-hepatology)
- Scrubs n Heels Mentorship Matrix (https://scrubsandheels.com/matrix/)
Providing Mentorship
The trainee authors on this manuscript describe in this section what has been helpful for them as mentees in the FELD research lab.
Student doctor Nguyen describes her experience as a lab member and things she finds most helpful as a medical student in the lab:
- Upon joining the team, a one-to-one meeting to discuss trainee’s personal and professional goals, and availability, was crucial to building the mentor-mentee relationship. Establishing this meaningful mentorship early on clarified expectations on both sides, built trust, and increased motivation. As a trainee, it is essential for me to see how my work aligns with a long-term goal and to receive ample guidance throughout the process.
- One of the most impactful experiences has been joining informal lunch sessions where trainees discussed data collection protocols and exchanged insights. In doing so, Dr. Feld has cultivated a lab culture that encourages curiosity, constructive feedback, and collaborative learning.
- To increase productivity, our team of trainees created a useful group message thread where we coordinated more sessions to collaborate. This coordination formed stronger relationships between team members and fostered a sense of shared purpose.
Dr. Cooper, a third year internal medicine resident, describes her experience as both a research mentee and a mentor to the junior trainees: “As a resident pursuing a career in academic gastroenterology and hepatology, I have found three key elements to be most helpful: intentional mentorship, structured meetings, and leadership development.”
- Intentional mentorship: Prior to joining the lab, I met with Dr. Feld to discuss my research experience and my goals. She took the time to understand these within the context of my training timeline and tailored project opportunities that aligned with my interests and were both feasible and impactful for my next steps. This intentional approach not only fostered a productive research experience but also established a mentor-mentee relationship built on genuine care for my growth and development.
- Regular meetings: Frequent lab meetings promote accountability, teamwork, and shared problem-solving skills. The open exchange of ideas fosters collaboration and joint problem solving to elevate the quality of our research. They are also an opportunity to observe key decision-making points during the research process and have been a great way to learn more about solid methodology.
- Supervised leadership: I have had ample time to lead discussions and coordinate projects among the junior trainees. These monitored leadership experiences promote project management skills, mentorship, and team dynamic awareness while maintaining the safety net of senior guidance. This model helped me transition from a trainee supporting others’ research to a more independent role, contributing to multi-disciplinary projects while mentoring junior members.
Conclusion
In conclusion, many exciting opportunities and notable barriers exist to establishing a clinical research laboratory in the early career. While excellence in each of the areas outlined may evolve, some aspects will come easier than others and with time, persistence, and a bit of luck, the research world will be a better place because of your contributions!
Dr. Feld is assistant professor of gastroenterology and hepatology and physician executive of Diversity, Equity, Inclusion and Belonging for the department of medicine at the University of Massachusetts (UMass) Chan Medical School, Worcester. Ms. Nguyen is a medical student at UMass Chan Medical School. Dr. Cooper is a resident physician at UMass Chan Medical School. Dr. Rabinowitz is an attending physician in the Inflammatory Bowel Disease Center at Beth Israel Deaconess Medical Center, Boston, Mass. Dr. Uchida is codirector of the Multidisciplinary Eosinophilic Gastrointestinal Disease Clinic at the University of Utah School of Medicine, Salt Lake City.
The Federal Trade Commission’s Non-Compete Ban
Non-compete agreements (NCAs) in physician contracts, also termed “restrictive covenants” or “covenants not to compete,” have become a hot topic recently because of the Federal Trade Commission’s (FTC’s) April 2024 ruling invalidating almost all NCAs. But in fact, NCAs have long been controversial, and no more so than in the realm of physician NCAs, which involve substantial policy concerns.
how it relates to a physician employment contract currently, and its possible evolution.
What is It?
Generally speaking, an NCA, usually in the form of an employment contract clause, is an agreement between the employer and the employee that the employee will not enter into post-contract competition with that employer within the limitations of a specific duration, scope of practice, and/or geography. NCAs have traditionally been regulated under state statutory law and common law and have been permitted based on policy considerations that attempt to balance competing employee and employer interests. Physicians should understand their states’ statutory treatment of an NCA.
NCAs protect important employer business interests, including the protection of proprietary information, safeguarding trade secrets, reducing employee turnover, and protecting patient lists. Employees, though, have limited mobility in changing professional positions, have less bargaining power with the employer, and may find themselves with limited options for comparable professional positions.
The NCA ostensibly appears to greatly benefit the employer’s interests over the employee’s; however, NCA protection of employer interests may also substantially benefit employees by encouraging substantial employer investment in employees whom the employer recognizes as a stable and likely long-term human resource, ultimately fostering increased employee satisfaction and innovation. Indeed, one concern with the FTC’s non-compete ban is the potential for significant underinvestment in information sharing and employee training, because employers would, without a NCA, be less likely to recoup those employee investments and would have limited ability to keep competitors from free-riding on investments in employees who leave and join competitors. Ultimately, this would lead to decreased market efficiency.
What is Its Status Today?
Regulation of NCAs, including physician NCAs, has traditionally been based on state statutory law and by common law. Perhaps because of the increasing use of the NCA in professional settings, the NCA has been increasingly scrutinized by courts and state legislatures in the last few decades, with an overall increasing focus on NCA reasonableness and appropriate fit in individual employment settings, and with an emphasis on employer demonstration of legitimate and significant business interests for using a NCA.
States have evolved differently in their treatment of NCAs; some states ban NCAs altogether while others allow them with varying interpretation and enforceability, frequently focused upon the NCA’s duration, scope, and geography. Similarly, in common law, courts will frequently invalidate NCAs that are found to be unreasonably overbroad, either geographically, temporally, and/or in regard to scope.
On April 23, 2024, however, the FTC altered this existing state of affairs by issuing a rule banning new NCAs in all employment situations after September 3, 2024. The rule also holds that existing NCAs are not enforceable, with a small carve-out for some senior executives. It applies to for-profit businesses, and some, but not all, non-profit organizations. The FTC’s stated intent is to reduce healthcare spending by increasing employee compensation and mobility. The FTC’s ban is likely meant to reduce transaction costs by increasing physician mobility.
There have been several lawsuits regarding the FTC ruling, challenging it on different grounds. The US District Court for the Northern District of Texas in Ryan LLC v. FTC issued first a preliminary injunction, then a final decision overturning the FTC’s rule. The Court held that the FTC had exceeded its statutory authority, and further, that the rule was arbitrary and capricious. It noted that the rule’s “categorical ban” has no equivalent in state law, is “unreasonably overbroad without a reasonable explanation,” “provides no evidence or reasoned basis,” does not “consider the positive benefits of non-compete agreements,” and does not “address alternatives to the Rule.” The Ryan Court reasoned that as an administrative agency, the FTC can only act as Congress authorizes by statute. On Oct. 18, 2024, the FTC appealed the Court’s decision to the Fifth Circuit Court of Appeals, seeking to reverse the holding setting aside its NCA ban.
The United States District Court for the Eastern District of Pennsylvania in ATS Tree Services LLC v. FTC denied the plaintiff’s motion to stay enforcement of the rule, refusing to issue a preliminary injunction preventing its implementation. As in Ryan, the ATS Tree Services LLC v. FTC plaintiffs argued that the FTC had exceeded its statutory authority in issuing the rule. However, the Plaintiff did not appeal the holding.
The US District Court for the Middle District of Florida in Properties of the Villages, Inc. v. FTCheld, like Ryan, that the rule exceeds the FTC’s statutory authority, noting the FTC’s prior lack of any NCA enforcement actions; however, its reasoning differed from Ryan. The Florida Court held that the FTC in fact has statutory authority to issue such rules; however, the Court held that the FTC could not enforce its rule because it violates the “major questions doctrine.” The “major questions doctrine” requires an agency such as the FTC to “point to clear congressional authorization” for any rule it issues that has “extraordinary ... economic and political significance,” as the NCA ban rule certainly does.
What is Its Future?
The FTC’s NCA ban remains unsettled. State legislatures, in response to the recent court holdings, are reassessing their statutory law regarding NCAs. The Ryan Court’s holding prevented the FTC’s rule from going into effect on September 4, 2024. The Texas and Florida court decisions are awaiting 5th and 11th Circuit Court of Appeals review, respectively. Assuming affirmation of either of the cases on appeal, a circuit split regarding the NCA ban may occur. The US Supreme Court may be called upon to determine the validity of the FTC rule banning NCAs. The Circuit Court decisions are likely to occur in 2025, and any Supreme Court decision would not likely occur until 2026. Meanwhile, state statutory law and common law still apply to NCAs, and the FTC may challenge the validity of NCAs on a case-by-case basis.
US antitrust law remains a potential remedy to scrutinize and restrain inappropriate business practices, including NCA-related abuses. The Sherman Act allows federal and state actors and private citizens, to sue for redress. Antitrust cases are typically considered using the “rule of reason” formulated by the Supreme Court in 1911, which requires plaintiffs show that defendant businesses possessing market power did in fact undertake anticompetitive conduct that had or likely had anticompetitive effects. In other words, the court in an antitrust case will require that the plaintiff show that the business actually had a significant controlling market presence in the geographic area; and further, that the plaintiff show that the business’ actions in fact had an anticompetitive effect, or likely had one. The latter can be found by showing an anticompetitive effect such as abusive pricing
The FTC’s ruling is legally and academically controversial and in fact may not withstand court scrutiny. The rule was put forth by the FTC as an ambitious rule to reduce healthcare spending. But businesses survive only if their revenue surpasses their costs, including personnel costs. Further, maximization of capitalization is attained when businesses require NCAs. Businesses invest heavily in recruiting, hiring, and training personnel, and increased personnel turnover increases these expenditures. NCAs arguably provide a collective benefit by ensuring force continuity, mitigating the risk of the loss of highly trained personnel with proprietary knowledge. NCAs also help a business maintain a skilled workforce, helping maximize business valuation. If FTC’s NCA ban rule were ultimately upheld, businesses would likely respond by instituting longer-term employee contracts, extended termination notice periods, and disincentives for employees who do not fully serve their contract length, including substantial financial disincentives. Business valuation might decrease, reducing investment incentives.
NCAs have long been a method of balancing the interests of employees and employers. They protect businesses’ confidential information, trade secrets, and patient lists, at some cost to employees pursuing new opportunities. The employee, though, is also provided with some benefit from the NCA, albeit indirect. State statutory law and courts have traditionally worked to ensure an appropriate delicate balance between interests, with courts generally finding unbalanced NCAs unenforceable.
For now, physicians should understand the policy considerations of and recognize the uncertainty surrounding NCAs, become familiar with their state’s statutory NCA law, review employment contracts carefully for NCA reasonableness, and seek legal advice if necessary.
Perhaps the FTC’s approach is the correct one for our future. Or perhaps the appropriate future of NCA interpretation and enforcement should continue to rest on state statutory law and common law, where antitrust enforcement is on a case-by-case basis, rather than FTC rulemaking. The results of high court decisions, state statutory law changes in response to the FTC rule, and perhaps US congressional action will provide the final answer.
Dr. Allen is based at the University of Oklahoma Health Sciences Center in Oklahoma City. He has declared no conflicts of interest in relation to this article.
Non-compete agreements (NCAs) in physician contracts, also termed “restrictive covenants” or “covenants not to compete,” have become a hot topic recently because of the Federal Trade Commission’s (FTC’s) April 2024 ruling invalidating almost all NCAs. But in fact, NCAs have long been controversial, and no more so than in the realm of physician NCAs, which involve substantial policy concerns.
how it relates to a physician employment contract currently, and its possible evolution.
What is It?
Generally speaking, an NCA, usually in the form of an employment contract clause, is an agreement between the employer and the employee that the employee will not enter into post-contract competition with that employer within the limitations of a specific duration, scope of practice, and/or geography. NCAs have traditionally been regulated under state statutory law and common law and have been permitted based on policy considerations that attempt to balance competing employee and employer interests. Physicians should understand their states’ statutory treatment of an NCA.
NCAs protect important employer business interests, including the protection of proprietary information, safeguarding trade secrets, reducing employee turnover, and protecting patient lists. Employees, though, have limited mobility in changing professional positions, have less bargaining power with the employer, and may find themselves with limited options for comparable professional positions.
The NCA ostensibly appears to greatly benefit the employer’s interests over the employee’s; however, NCA protection of employer interests may also substantially benefit employees by encouraging substantial employer investment in employees whom the employer recognizes as a stable and likely long-term human resource, ultimately fostering increased employee satisfaction and innovation. Indeed, one concern with the FTC’s non-compete ban is the potential for significant underinvestment in information sharing and employee training, because employers would, without a NCA, be less likely to recoup those employee investments and would have limited ability to keep competitors from free-riding on investments in employees who leave and join competitors. Ultimately, this would lead to decreased market efficiency.
What is Its Status Today?
Regulation of NCAs, including physician NCAs, has traditionally been based on state statutory law and by common law. Perhaps because of the increasing use of the NCA in professional settings, the NCA has been increasingly scrutinized by courts and state legislatures in the last few decades, with an overall increasing focus on NCA reasonableness and appropriate fit in individual employment settings, and with an emphasis on employer demonstration of legitimate and significant business interests for using a NCA.
States have evolved differently in their treatment of NCAs; some states ban NCAs altogether while others allow them with varying interpretation and enforceability, frequently focused upon the NCA’s duration, scope, and geography. Similarly, in common law, courts will frequently invalidate NCAs that are found to be unreasonably overbroad, either geographically, temporally, and/or in regard to scope.
On April 23, 2024, however, the FTC altered this existing state of affairs by issuing a rule banning new NCAs in all employment situations after September 3, 2024. The rule also holds that existing NCAs are not enforceable, with a small carve-out for some senior executives. It applies to for-profit businesses, and some, but not all, non-profit organizations. The FTC’s stated intent is to reduce healthcare spending by increasing employee compensation and mobility. The FTC’s ban is likely meant to reduce transaction costs by increasing physician mobility.
There have been several lawsuits regarding the FTC ruling, challenging it on different grounds. The US District Court for the Northern District of Texas in Ryan LLC v. FTC issued first a preliminary injunction, then a final decision overturning the FTC’s rule. The Court held that the FTC had exceeded its statutory authority, and further, that the rule was arbitrary and capricious. It noted that the rule’s “categorical ban” has no equivalent in state law, is “unreasonably overbroad without a reasonable explanation,” “provides no evidence or reasoned basis,” does not “consider the positive benefits of non-compete agreements,” and does not “address alternatives to the Rule.” The Ryan Court reasoned that as an administrative agency, the FTC can only act as Congress authorizes by statute. On Oct. 18, 2024, the FTC appealed the Court’s decision to the Fifth Circuit Court of Appeals, seeking to reverse the holding setting aside its NCA ban.
The United States District Court for the Eastern District of Pennsylvania in ATS Tree Services LLC v. FTC denied the plaintiff’s motion to stay enforcement of the rule, refusing to issue a preliminary injunction preventing its implementation. As in Ryan, the ATS Tree Services LLC v. FTC plaintiffs argued that the FTC had exceeded its statutory authority in issuing the rule. However, the Plaintiff did not appeal the holding.
The US District Court for the Middle District of Florida in Properties of the Villages, Inc. v. FTCheld, like Ryan, that the rule exceeds the FTC’s statutory authority, noting the FTC’s prior lack of any NCA enforcement actions; however, its reasoning differed from Ryan. The Florida Court held that the FTC in fact has statutory authority to issue such rules; however, the Court held that the FTC could not enforce its rule because it violates the “major questions doctrine.” The “major questions doctrine” requires an agency such as the FTC to “point to clear congressional authorization” for any rule it issues that has “extraordinary ... economic and political significance,” as the NCA ban rule certainly does.
What is Its Future?
The FTC’s NCA ban remains unsettled. State legislatures, in response to the recent court holdings, are reassessing their statutory law regarding NCAs. The Ryan Court’s holding prevented the FTC’s rule from going into effect on September 4, 2024. The Texas and Florida court decisions are awaiting 5th and 11th Circuit Court of Appeals review, respectively. Assuming affirmation of either of the cases on appeal, a circuit split regarding the NCA ban may occur. The US Supreme Court may be called upon to determine the validity of the FTC rule banning NCAs. The Circuit Court decisions are likely to occur in 2025, and any Supreme Court decision would not likely occur until 2026. Meanwhile, state statutory law and common law still apply to NCAs, and the FTC may challenge the validity of NCAs on a case-by-case basis.
US antitrust law remains a potential remedy to scrutinize and restrain inappropriate business practices, including NCA-related abuses. The Sherman Act allows federal and state actors and private citizens, to sue for redress. Antitrust cases are typically considered using the “rule of reason” formulated by the Supreme Court in 1911, which requires plaintiffs show that defendant businesses possessing market power did in fact undertake anticompetitive conduct that had or likely had anticompetitive effects. In other words, the court in an antitrust case will require that the plaintiff show that the business actually had a significant controlling market presence in the geographic area; and further, that the plaintiff show that the business’ actions in fact had an anticompetitive effect, or likely had one. The latter can be found by showing an anticompetitive effect such as abusive pricing
The FTC’s ruling is legally and academically controversial and in fact may not withstand court scrutiny. The rule was put forth by the FTC as an ambitious rule to reduce healthcare spending. But businesses survive only if their revenue surpasses their costs, including personnel costs. Further, maximization of capitalization is attained when businesses require NCAs. Businesses invest heavily in recruiting, hiring, and training personnel, and increased personnel turnover increases these expenditures. NCAs arguably provide a collective benefit by ensuring force continuity, mitigating the risk of the loss of highly trained personnel with proprietary knowledge. NCAs also help a business maintain a skilled workforce, helping maximize business valuation. If FTC’s NCA ban rule were ultimately upheld, businesses would likely respond by instituting longer-term employee contracts, extended termination notice periods, and disincentives for employees who do not fully serve their contract length, including substantial financial disincentives. Business valuation might decrease, reducing investment incentives.
NCAs have long been a method of balancing the interests of employees and employers. They protect businesses’ confidential information, trade secrets, and patient lists, at some cost to employees pursuing new opportunities. The employee, though, is also provided with some benefit from the NCA, albeit indirect. State statutory law and courts have traditionally worked to ensure an appropriate delicate balance between interests, with courts generally finding unbalanced NCAs unenforceable.
For now, physicians should understand the policy considerations of and recognize the uncertainty surrounding NCAs, become familiar with their state’s statutory NCA law, review employment contracts carefully for NCA reasonableness, and seek legal advice if necessary.
Perhaps the FTC’s approach is the correct one for our future. Or perhaps the appropriate future of NCA interpretation and enforcement should continue to rest on state statutory law and common law, where antitrust enforcement is on a case-by-case basis, rather than FTC rulemaking. The results of high court decisions, state statutory law changes in response to the FTC rule, and perhaps US congressional action will provide the final answer.
Dr. Allen is based at the University of Oklahoma Health Sciences Center in Oklahoma City. He has declared no conflicts of interest in relation to this article.
Non-compete agreements (NCAs) in physician contracts, also termed “restrictive covenants” or “covenants not to compete,” have become a hot topic recently because of the Federal Trade Commission’s (FTC’s) April 2024 ruling invalidating almost all NCAs. But in fact, NCAs have long been controversial, and no more so than in the realm of physician NCAs, which involve substantial policy concerns.
how it relates to a physician employment contract currently, and its possible evolution.
What is It?
Generally speaking, an NCA, usually in the form of an employment contract clause, is an agreement between the employer and the employee that the employee will not enter into post-contract competition with that employer within the limitations of a specific duration, scope of practice, and/or geography. NCAs have traditionally been regulated under state statutory law and common law and have been permitted based on policy considerations that attempt to balance competing employee and employer interests. Physicians should understand their states’ statutory treatment of an NCA.
NCAs protect important employer business interests, including the protection of proprietary information, safeguarding trade secrets, reducing employee turnover, and protecting patient lists. Employees, though, have limited mobility in changing professional positions, have less bargaining power with the employer, and may find themselves with limited options for comparable professional positions.
The NCA ostensibly appears to greatly benefit the employer’s interests over the employee’s; however, NCA protection of employer interests may also substantially benefit employees by encouraging substantial employer investment in employees whom the employer recognizes as a stable and likely long-term human resource, ultimately fostering increased employee satisfaction and innovation. Indeed, one concern with the FTC’s non-compete ban is the potential for significant underinvestment in information sharing and employee training, because employers would, without a NCA, be less likely to recoup those employee investments and would have limited ability to keep competitors from free-riding on investments in employees who leave and join competitors. Ultimately, this would lead to decreased market efficiency.
What is Its Status Today?
Regulation of NCAs, including physician NCAs, has traditionally been based on state statutory law and by common law. Perhaps because of the increasing use of the NCA in professional settings, the NCA has been increasingly scrutinized by courts and state legislatures in the last few decades, with an overall increasing focus on NCA reasonableness and appropriate fit in individual employment settings, and with an emphasis on employer demonstration of legitimate and significant business interests for using a NCA.
States have evolved differently in their treatment of NCAs; some states ban NCAs altogether while others allow them with varying interpretation and enforceability, frequently focused upon the NCA’s duration, scope, and geography. Similarly, in common law, courts will frequently invalidate NCAs that are found to be unreasonably overbroad, either geographically, temporally, and/or in regard to scope.
On April 23, 2024, however, the FTC altered this existing state of affairs by issuing a rule banning new NCAs in all employment situations after September 3, 2024. The rule also holds that existing NCAs are not enforceable, with a small carve-out for some senior executives. It applies to for-profit businesses, and some, but not all, non-profit organizations. The FTC’s stated intent is to reduce healthcare spending by increasing employee compensation and mobility. The FTC’s ban is likely meant to reduce transaction costs by increasing physician mobility.
There have been several lawsuits regarding the FTC ruling, challenging it on different grounds. The US District Court for the Northern District of Texas in Ryan LLC v. FTC issued first a preliminary injunction, then a final decision overturning the FTC’s rule. The Court held that the FTC had exceeded its statutory authority, and further, that the rule was arbitrary and capricious. It noted that the rule’s “categorical ban” has no equivalent in state law, is “unreasonably overbroad without a reasonable explanation,” “provides no evidence or reasoned basis,” does not “consider the positive benefits of non-compete agreements,” and does not “address alternatives to the Rule.” The Ryan Court reasoned that as an administrative agency, the FTC can only act as Congress authorizes by statute. On Oct. 18, 2024, the FTC appealed the Court’s decision to the Fifth Circuit Court of Appeals, seeking to reverse the holding setting aside its NCA ban.
The United States District Court for the Eastern District of Pennsylvania in ATS Tree Services LLC v. FTC denied the plaintiff’s motion to stay enforcement of the rule, refusing to issue a preliminary injunction preventing its implementation. As in Ryan, the ATS Tree Services LLC v. FTC plaintiffs argued that the FTC had exceeded its statutory authority in issuing the rule. However, the Plaintiff did not appeal the holding.
The US District Court for the Middle District of Florida in Properties of the Villages, Inc. v. FTCheld, like Ryan, that the rule exceeds the FTC’s statutory authority, noting the FTC’s prior lack of any NCA enforcement actions; however, its reasoning differed from Ryan. The Florida Court held that the FTC in fact has statutory authority to issue such rules; however, the Court held that the FTC could not enforce its rule because it violates the “major questions doctrine.” The “major questions doctrine” requires an agency such as the FTC to “point to clear congressional authorization” for any rule it issues that has “extraordinary ... economic and political significance,” as the NCA ban rule certainly does.
What is Its Future?
The FTC’s NCA ban remains unsettled. State legislatures, in response to the recent court holdings, are reassessing their statutory law regarding NCAs. The Ryan Court’s holding prevented the FTC’s rule from going into effect on September 4, 2024. The Texas and Florida court decisions are awaiting 5th and 11th Circuit Court of Appeals review, respectively. Assuming affirmation of either of the cases on appeal, a circuit split regarding the NCA ban may occur. The US Supreme Court may be called upon to determine the validity of the FTC rule banning NCAs. The Circuit Court decisions are likely to occur in 2025, and any Supreme Court decision would not likely occur until 2026. Meanwhile, state statutory law and common law still apply to NCAs, and the FTC may challenge the validity of NCAs on a case-by-case basis.
US antitrust law remains a potential remedy to scrutinize and restrain inappropriate business practices, including NCA-related abuses. The Sherman Act allows federal and state actors and private citizens, to sue for redress. Antitrust cases are typically considered using the “rule of reason” formulated by the Supreme Court in 1911, which requires plaintiffs show that defendant businesses possessing market power did in fact undertake anticompetitive conduct that had or likely had anticompetitive effects. In other words, the court in an antitrust case will require that the plaintiff show that the business actually had a significant controlling market presence in the geographic area; and further, that the plaintiff show that the business’ actions in fact had an anticompetitive effect, or likely had one. The latter can be found by showing an anticompetitive effect such as abusive pricing
The FTC’s ruling is legally and academically controversial and in fact may not withstand court scrutiny. The rule was put forth by the FTC as an ambitious rule to reduce healthcare spending. But businesses survive only if their revenue surpasses their costs, including personnel costs. Further, maximization of capitalization is attained when businesses require NCAs. Businesses invest heavily in recruiting, hiring, and training personnel, and increased personnel turnover increases these expenditures. NCAs arguably provide a collective benefit by ensuring force continuity, mitigating the risk of the loss of highly trained personnel with proprietary knowledge. NCAs also help a business maintain a skilled workforce, helping maximize business valuation. If FTC’s NCA ban rule were ultimately upheld, businesses would likely respond by instituting longer-term employee contracts, extended termination notice periods, and disincentives for employees who do not fully serve their contract length, including substantial financial disincentives. Business valuation might decrease, reducing investment incentives.
NCAs have long been a method of balancing the interests of employees and employers. They protect businesses’ confidential information, trade secrets, and patient lists, at some cost to employees pursuing new opportunities. The employee, though, is also provided with some benefit from the NCA, albeit indirect. State statutory law and courts have traditionally worked to ensure an appropriate delicate balance between interests, with courts generally finding unbalanced NCAs unenforceable.
For now, physicians should understand the policy considerations of and recognize the uncertainty surrounding NCAs, become familiar with their state’s statutory NCA law, review employment contracts carefully for NCA reasonableness, and seek legal advice if necessary.
Perhaps the FTC’s approach is the correct one for our future. Or perhaps the appropriate future of NCA interpretation and enforcement should continue to rest on state statutory law and common law, where antitrust enforcement is on a case-by-case basis, rather than FTC rulemaking. The results of high court decisions, state statutory law changes in response to the FTC rule, and perhaps US congressional action will provide the final answer.
Dr. Allen is based at the University of Oklahoma Health Sciences Center in Oklahoma City. He has declared no conflicts of interest in relation to this article.
Collins Confirmed as VA Secretary
Collins Confirmed as VA Secretary
The U.S. Senate confirmed former Georgia congressman Doug Collins as the Secretary for the US Department of Veterans Affairs (VA) on Feb. 4 in a comfortable 77 to 23 vote. Collins received votes from every Republican Senator and 23 Democratic Senators.
“The MISSION Act, the VA Accountability and Whistleblower Protection Act and the PACT Act are 3 of the most important veterans laws in recent history,” Collins said during his confirmation hearing. “They received widespread bipartisan support because their focus is exactly where VA’s focus should be: on veteran convenience and accountability for the department.”
Collins pledged to keep the VA strong but also to expand community care, noting: “I believe you can have both, you can have a strong VA as it currently exists, and you can have the community care aspect.”
Sen. Richard Blumenthal (D-CT), who voted to confirm Collins, urged the secretary to exempt all VA employees from the Trump Administration’s recent hiring freeze; ensure that financial assistance programs for veterans are exempt from funding pauses; work with President Trump to reappoint VA Inspector General Mike Missal, who was removed from office by the President in January; and to ensure all VA employees receive due process amid recent directives from the Office of Personnel Management.
The VA also announced a number of new political appointees, including Chris Syrek, who set to serve as chief of staff; Cheryl Mason is slated to serve as senior advisory to Secretary Collins; and Lynda Davis is set to serve as the chief officer with VA's Veterans Experience Office. No nominations have been made for the Undersecretary of Health to date.
The U.S. Senate confirmed former Georgia congressman Doug Collins as the Secretary for the US Department of Veterans Affairs (VA) on Feb. 4 in a comfortable 77 to 23 vote. Collins received votes from every Republican Senator and 23 Democratic Senators.
“The MISSION Act, the VA Accountability and Whistleblower Protection Act and the PACT Act are 3 of the most important veterans laws in recent history,” Collins said during his confirmation hearing. “They received widespread bipartisan support because their focus is exactly where VA’s focus should be: on veteran convenience and accountability for the department.”
Collins pledged to keep the VA strong but also to expand community care, noting: “I believe you can have both, you can have a strong VA as it currently exists, and you can have the community care aspect.”
Sen. Richard Blumenthal (D-CT), who voted to confirm Collins, urged the secretary to exempt all VA employees from the Trump Administration’s recent hiring freeze; ensure that financial assistance programs for veterans are exempt from funding pauses; work with President Trump to reappoint VA Inspector General Mike Missal, who was removed from office by the President in January; and to ensure all VA employees receive due process amid recent directives from the Office of Personnel Management.
The VA also announced a number of new political appointees, including Chris Syrek, who set to serve as chief of staff; Cheryl Mason is slated to serve as senior advisory to Secretary Collins; and Lynda Davis is set to serve as the chief officer with VA's Veterans Experience Office. No nominations have been made for the Undersecretary of Health to date.
The U.S. Senate confirmed former Georgia congressman Doug Collins as the Secretary for the US Department of Veterans Affairs (VA) on Feb. 4 in a comfortable 77 to 23 vote. Collins received votes from every Republican Senator and 23 Democratic Senators.
“The MISSION Act, the VA Accountability and Whistleblower Protection Act and the PACT Act are 3 of the most important veterans laws in recent history,” Collins said during his confirmation hearing. “They received widespread bipartisan support because their focus is exactly where VA’s focus should be: on veteran convenience and accountability for the department.”
Collins pledged to keep the VA strong but also to expand community care, noting: “I believe you can have both, you can have a strong VA as it currently exists, and you can have the community care aspect.”
Sen. Richard Blumenthal (D-CT), who voted to confirm Collins, urged the secretary to exempt all VA employees from the Trump Administration’s recent hiring freeze; ensure that financial assistance programs for veterans are exempt from funding pauses; work with President Trump to reappoint VA Inspector General Mike Missal, who was removed from office by the President in January; and to ensure all VA employees receive due process amid recent directives from the Office of Personnel Management.
The VA also announced a number of new political appointees, including Chris Syrek, who set to serve as chief of staff; Cheryl Mason is slated to serve as senior advisory to Secretary Collins; and Lynda Davis is set to serve as the chief officer with VA's Veterans Experience Office. No nominations have been made for the Undersecretary of Health to date.
Collins Confirmed as VA Secretary
Collins Confirmed as VA Secretary
Impact of Return to Office on VA Telehealth Remains Unclear
Nearly 96,000 US Department of Veterans Affairs (VA) employees—about 20% of the workforce—will be required to return to in-office work by the end of February. The announcement follows a Jan. 20 presidential memorandum, which states agency heads must “take all necessary steps to terminate remote work arrangements and require employees to return to work in-person at their respective duty stations on a full-time basis.” According to a Jan. 28 email sent from the Office of Personnel Management but without a signature, federal employees who refuse will be offered “dignified, fair departure from the federal government utilizing a deferred resignation program.”
The revised VA work policy states “eligible employees must work full-time at their respective duty stations (agency worksites) unless excused due to a disability, qualifying medical condition or other compelling reason.” All nonbargaining unit employees and supervisors who are within 50 miles of their office have until Feb. 24 to return. The VA stated that further guidance is coming for those who live > 50 miles from a facility.
“VA’s policy allows exceptions for arrangements approved for employees as a reasonable accommodation due to a disability or a qualifying medical condition. Exceptions may also be allowed for military spouses with permanent change of station orders,” according to a VA press release.
“This is a commonsense step toward treating all VA employees equally,” acting VA Secretary Todd Hunter said. “Most VA clinical staff don’t have the luxury of working remotely, and we believe the performance, collaboration and productivity of the department will improve if all VA employees are held to the same standard.”
The impact on Veterans Health Administration operations remains difficult to determine. The order appears to include personnel providing telehealth care from remote locations, including those at the Clinical Resource Hub (CRH) program. CRH uses a hub and spoke model for limited time primary care and mental health care staffing to cover local clinician vacancies. CRH clinicians have provided > 500,000 veterans with care, averaging > 25,000 encounters in the program’s first year. Started during fiscal year 2020 amid the COVID-19 pandemic, CRH employed 636 clinicians, but more recent data are not available. The VA provided > 28 million telehealth sessions to veterans across all of its telehealth modalities in 2023. Details on how many CRH clinicians and other telehealth practitioners work remotely are also not available.
On Feb. 3, the Office of Personnel Management issued a memo to federal agency heads arguing that any collective bargaining agreements that include teleworking may “conflict with management rights” and therefore may be “unlawful and cannot be enforced.”
The American Federation of Government Employees (AFGE), which represents 800,000 federal employees, disputed the memo. “Federal employees should know that approved union contracts are enforceable by law, and the President does not have the authority to make unilateral changes to those agreements,” AFGE President Everett Kelley said. “AFGE members will not be intimidated. If our contracts are violated, we will aggressively defend them.”
The VA must decide where to put the more than 47,000 workers who may be coming back. According to the Government Accountability Office, “Federal agencies have long struggled to determine how much office space they needed to fulfill their missions efficiently.” The VA has reduced its office space by > 290,000 ft2 over the last few years in the National Capital Region alone.
In his confirmation hearing last month, VA Secretary nominee Doug Collins told lawmakers that, if confirmed, he would “encourage employees to come back to work,” but he also said he would ensure the department was following the White House’s remote work limits. “We’re going to make sure that we get people in there,” he said, “because at the end of the day, it’s about veterans.”
Nearly 96,000 US Department of Veterans Affairs (VA) employees—about 20% of the workforce—will be required to return to in-office work by the end of February. The announcement follows a Jan. 20 presidential memorandum, which states agency heads must “take all necessary steps to terminate remote work arrangements and require employees to return to work in-person at their respective duty stations on a full-time basis.” According to a Jan. 28 email sent from the Office of Personnel Management but without a signature, federal employees who refuse will be offered “dignified, fair departure from the federal government utilizing a deferred resignation program.”
The revised VA work policy states “eligible employees must work full-time at their respective duty stations (agency worksites) unless excused due to a disability, qualifying medical condition or other compelling reason.” All nonbargaining unit employees and supervisors who are within 50 miles of their office have until Feb. 24 to return. The VA stated that further guidance is coming for those who live > 50 miles from a facility.
“VA’s policy allows exceptions for arrangements approved for employees as a reasonable accommodation due to a disability or a qualifying medical condition. Exceptions may also be allowed for military spouses with permanent change of station orders,” according to a VA press release.
“This is a commonsense step toward treating all VA employees equally,” acting VA Secretary Todd Hunter said. “Most VA clinical staff don’t have the luxury of working remotely, and we believe the performance, collaboration and productivity of the department will improve if all VA employees are held to the same standard.”
The impact on Veterans Health Administration operations remains difficult to determine. The order appears to include personnel providing telehealth care from remote locations, including those at the Clinical Resource Hub (CRH) program. CRH uses a hub and spoke model for limited time primary care and mental health care staffing to cover local clinician vacancies. CRH clinicians have provided > 500,000 veterans with care, averaging > 25,000 encounters in the program’s first year. Started during fiscal year 2020 amid the COVID-19 pandemic, CRH employed 636 clinicians, but more recent data are not available. The VA provided > 28 million telehealth sessions to veterans across all of its telehealth modalities in 2023. Details on how many CRH clinicians and other telehealth practitioners work remotely are also not available.
On Feb. 3, the Office of Personnel Management issued a memo to federal agency heads arguing that any collective bargaining agreements that include teleworking may “conflict with management rights” and therefore may be “unlawful and cannot be enforced.”
The American Federation of Government Employees (AFGE), which represents 800,000 federal employees, disputed the memo. “Federal employees should know that approved union contracts are enforceable by law, and the President does not have the authority to make unilateral changes to those agreements,” AFGE President Everett Kelley said. “AFGE members will not be intimidated. If our contracts are violated, we will aggressively defend them.”
The VA must decide where to put the more than 47,000 workers who may be coming back. According to the Government Accountability Office, “Federal agencies have long struggled to determine how much office space they needed to fulfill their missions efficiently.” The VA has reduced its office space by > 290,000 ft2 over the last few years in the National Capital Region alone.
In his confirmation hearing last month, VA Secretary nominee Doug Collins told lawmakers that, if confirmed, he would “encourage employees to come back to work,” but he also said he would ensure the department was following the White House’s remote work limits. “We’re going to make sure that we get people in there,” he said, “because at the end of the day, it’s about veterans.”
Nearly 96,000 US Department of Veterans Affairs (VA) employees—about 20% of the workforce—will be required to return to in-office work by the end of February. The announcement follows a Jan. 20 presidential memorandum, which states agency heads must “take all necessary steps to terminate remote work arrangements and require employees to return to work in-person at their respective duty stations on a full-time basis.” According to a Jan. 28 email sent from the Office of Personnel Management but without a signature, federal employees who refuse will be offered “dignified, fair departure from the federal government utilizing a deferred resignation program.”
The revised VA work policy states “eligible employees must work full-time at their respective duty stations (agency worksites) unless excused due to a disability, qualifying medical condition or other compelling reason.” All nonbargaining unit employees and supervisors who are within 50 miles of their office have until Feb. 24 to return. The VA stated that further guidance is coming for those who live > 50 miles from a facility.
“VA’s policy allows exceptions for arrangements approved for employees as a reasonable accommodation due to a disability or a qualifying medical condition. Exceptions may also be allowed for military spouses with permanent change of station orders,” according to a VA press release.
“This is a commonsense step toward treating all VA employees equally,” acting VA Secretary Todd Hunter said. “Most VA clinical staff don’t have the luxury of working remotely, and we believe the performance, collaboration and productivity of the department will improve if all VA employees are held to the same standard.”
The impact on Veterans Health Administration operations remains difficult to determine. The order appears to include personnel providing telehealth care from remote locations, including those at the Clinical Resource Hub (CRH) program. CRH uses a hub and spoke model for limited time primary care and mental health care staffing to cover local clinician vacancies. CRH clinicians have provided > 500,000 veterans with care, averaging > 25,000 encounters in the program’s first year. Started during fiscal year 2020 amid the COVID-19 pandemic, CRH employed 636 clinicians, but more recent data are not available. The VA provided > 28 million telehealth sessions to veterans across all of its telehealth modalities in 2023. Details on how many CRH clinicians and other telehealth practitioners work remotely are also not available.
On Feb. 3, the Office of Personnel Management issued a memo to federal agency heads arguing that any collective bargaining agreements that include teleworking may “conflict with management rights” and therefore may be “unlawful and cannot be enforced.”
The American Federation of Government Employees (AFGE), which represents 800,000 federal employees, disputed the memo. “Federal employees should know that approved union contracts are enforceable by law, and the President does not have the authority to make unilateral changes to those agreements,” AFGE President Everett Kelley said. “AFGE members will not be intimidated. If our contracts are violated, we will aggressively defend them.”
The VA must decide where to put the more than 47,000 workers who may be coming back. According to the Government Accountability Office, “Federal agencies have long struggled to determine how much office space they needed to fulfill their missions efficiently.” The VA has reduced its office space by > 290,000 ft2 over the last few years in the National Capital Region alone.
In his confirmation hearing last month, VA Secretary nominee Doug Collins told lawmakers that, if confirmed, he would “encourage employees to come back to work,” but he also said he would ensure the department was following the White House’s remote work limits. “We’re going to make sure that we get people in there,” he said, “because at the end of the day, it’s about veterans.”
Postoperative RT Plus Cetuximab Showed Mixed Results in Head and Neck Cancer Trial
TOPLINE:
Adding cetuximab (C) to postoperative radiotherapy (RT) improves disease-free survival (DFS) but not overall survival (OS) in intermediate-risk squamous cell carcinoma of the head and neck. Benefits were specifically observed in human papillomavirus–negative patients, who represented 80.2% of the study participants.
METHODOLOGY:
- Previous research showed that adding high-dose cisplatin to postoperative RT in patients with squamous cell carcinoma of the head and neck (SCCHN) improved outcomes in those with positive margins and nodal extracapsular extension of the tumor.
- The new phase 3 randomized trial, which enrolled patients from November 2009 to March 2018 included 577 individuals with resected SCCHN of the oral cavity, oropharynx, or larynx, specifically.
- Participants were randomly assigned 1:1 to receive either intensity-modulated RT (60-66 Gy) with weekly C (400 mg/m2 loading dose, followed by 250 mg/m2 weekly) or RT alone.
- The primary endpoint was OS in randomly assigned eligible patients, with DFS and toxicity as secondary endpoints.
- Analysis included stratified log-rank test for OS and DFS, while toxicity was compared using Fisher’s exact test.
TAKEAWAY:
- OS was not significantly improved with RT plus C vs RT alone (hazard ratio [HR], 0.81; 95% CI, 0.60-1.08; P = .0747), though 5-year OS rates were 76.5% vs 68.7%.
- DFS showed significant improvement with combined therapy (HR, 0.75; 95% CI, 0.57-0.98; P = .0168), with 5-year rates of 71.7% vs 63.6%.
- Grade 3-4 acute toxicity rates were significantly higher with combination therapy (70.3% vs 39.7%; P < .0001), primarily affecting skin and mucosa, though late toxicity rates were similar (33.2% vs 29.0%; P = .3101).
- The benefit of RT plus C was only observed in those patients who were human papillomavirus–negative, which comprised 80.2% of trial participants.
IN PRACTICE:
RT plus C “significantly improved DFS, but not OS, with no increase in long-term toxicity, compared with RT alone for resected, intermediate-risk SCCHN. RT plus C is an appropriate option for carefully selected patients with HPV-negative disease,” the authors of the study wrote.
SOURCE:
This study was led by Mitchell Machtay, MD, Penn State Health Milton S. Hershey Medical Center in Hershey, Pennsylvania. It was published online in Journal of Clinical Oncology.
LIMITATIONS:
According to the researchers, the OS in the control group was higher than predicted, resulting in the trial being underpowered to detect the initial targeted HR. The authors noted that the better-than-expected survival rates could be attributed to improvements in surgical and radiotherapeutic techniques, including mandatory intensity-modulated RT for all patients. Additionally, the researchers pointed out that patient selection may have influenced outcomes, as only 30% of study participants had more than two risk factors.
DISCLOSURES:
This study was supported by grants from the US National Cancer Institute and Eli Lilly Inc. Machtay received grants from Lilly/ImClone, AstraZeneca, and Merck Sharp & Dohme. Additional disclosures are noted in the original article.
This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.
TOPLINE:
Adding cetuximab (C) to postoperative radiotherapy (RT) improves disease-free survival (DFS) but not overall survival (OS) in intermediate-risk squamous cell carcinoma of the head and neck. Benefits were specifically observed in human papillomavirus–negative patients, who represented 80.2% of the study participants.
METHODOLOGY:
- Previous research showed that adding high-dose cisplatin to postoperative RT in patients with squamous cell carcinoma of the head and neck (SCCHN) improved outcomes in those with positive margins and nodal extracapsular extension of the tumor.
- The new phase 3 randomized trial, which enrolled patients from November 2009 to March 2018 included 577 individuals with resected SCCHN of the oral cavity, oropharynx, or larynx, specifically.
- Participants were randomly assigned 1:1 to receive either intensity-modulated RT (60-66 Gy) with weekly C (400 mg/m2 loading dose, followed by 250 mg/m2 weekly) or RT alone.
- The primary endpoint was OS in randomly assigned eligible patients, with DFS and toxicity as secondary endpoints.
- Analysis included stratified log-rank test for OS and DFS, while toxicity was compared using Fisher’s exact test.
TAKEAWAY:
- OS was not significantly improved with RT plus C vs RT alone (hazard ratio [HR], 0.81; 95% CI, 0.60-1.08; P = .0747), though 5-year OS rates were 76.5% vs 68.7%.
- DFS showed significant improvement with combined therapy (HR, 0.75; 95% CI, 0.57-0.98; P = .0168), with 5-year rates of 71.7% vs 63.6%.
- Grade 3-4 acute toxicity rates were significantly higher with combination therapy (70.3% vs 39.7%; P < .0001), primarily affecting skin and mucosa, though late toxicity rates were similar (33.2% vs 29.0%; P = .3101).
- The benefit of RT plus C was only observed in those patients who were human papillomavirus–negative, which comprised 80.2% of trial participants.
IN PRACTICE:
RT plus C “significantly improved DFS, but not OS, with no increase in long-term toxicity, compared with RT alone for resected, intermediate-risk SCCHN. RT plus C is an appropriate option for carefully selected patients with HPV-negative disease,” the authors of the study wrote.
SOURCE:
This study was led by Mitchell Machtay, MD, Penn State Health Milton S. Hershey Medical Center in Hershey, Pennsylvania. It was published online in Journal of Clinical Oncology.
LIMITATIONS:
According to the researchers, the OS in the control group was higher than predicted, resulting in the trial being underpowered to detect the initial targeted HR. The authors noted that the better-than-expected survival rates could be attributed to improvements in surgical and radiotherapeutic techniques, including mandatory intensity-modulated RT for all patients. Additionally, the researchers pointed out that patient selection may have influenced outcomes, as only 30% of study participants had more than two risk factors.
DISCLOSURES:
This study was supported by grants from the US National Cancer Institute and Eli Lilly Inc. Machtay received grants from Lilly/ImClone, AstraZeneca, and Merck Sharp & Dohme. Additional disclosures are noted in the original article.
This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.
TOPLINE:
Adding cetuximab (C) to postoperative radiotherapy (RT) improves disease-free survival (DFS) but not overall survival (OS) in intermediate-risk squamous cell carcinoma of the head and neck. Benefits were specifically observed in human papillomavirus–negative patients, who represented 80.2% of the study participants.
METHODOLOGY:
- Previous research showed that adding high-dose cisplatin to postoperative RT in patients with squamous cell carcinoma of the head and neck (SCCHN) improved outcomes in those with positive margins and nodal extracapsular extension of the tumor.
- The new phase 3 randomized trial, which enrolled patients from November 2009 to March 2018 included 577 individuals with resected SCCHN of the oral cavity, oropharynx, or larynx, specifically.
- Participants were randomly assigned 1:1 to receive either intensity-modulated RT (60-66 Gy) with weekly C (400 mg/m2 loading dose, followed by 250 mg/m2 weekly) or RT alone.
- The primary endpoint was OS in randomly assigned eligible patients, with DFS and toxicity as secondary endpoints.
- Analysis included stratified log-rank test for OS and DFS, while toxicity was compared using Fisher’s exact test.
TAKEAWAY:
- OS was not significantly improved with RT plus C vs RT alone (hazard ratio [HR], 0.81; 95% CI, 0.60-1.08; P = .0747), though 5-year OS rates were 76.5% vs 68.7%.
- DFS showed significant improvement with combined therapy (HR, 0.75; 95% CI, 0.57-0.98; P = .0168), with 5-year rates of 71.7% vs 63.6%.
- Grade 3-4 acute toxicity rates were significantly higher with combination therapy (70.3% vs 39.7%; P < .0001), primarily affecting skin and mucosa, though late toxicity rates were similar (33.2% vs 29.0%; P = .3101).
- The benefit of RT plus C was only observed in those patients who were human papillomavirus–negative, which comprised 80.2% of trial participants.
IN PRACTICE:
RT plus C “significantly improved DFS, but not OS, with no increase in long-term toxicity, compared with RT alone for resected, intermediate-risk SCCHN. RT plus C is an appropriate option for carefully selected patients with HPV-negative disease,” the authors of the study wrote.
SOURCE:
This study was led by Mitchell Machtay, MD, Penn State Health Milton S. Hershey Medical Center in Hershey, Pennsylvania. It was published online in Journal of Clinical Oncology.
LIMITATIONS:
According to the researchers, the OS in the control group was higher than predicted, resulting in the trial being underpowered to detect the initial targeted HR. The authors noted that the better-than-expected survival rates could be attributed to improvements in surgical and radiotherapeutic techniques, including mandatory intensity-modulated RT for all patients. Additionally, the researchers pointed out that patient selection may have influenced outcomes, as only 30% of study participants had more than two risk factors.
DISCLOSURES:
This study was supported by grants from the US National Cancer Institute and Eli Lilly Inc. Machtay received grants from Lilly/ImClone, AstraZeneca, and Merck Sharp & Dohme. Additional disclosures are noted in the original article.
This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.